Biochemical and biophysical research communications最新文献_第6页

HAP/ClpP-mediated disaggregation and degradation of Mutant SOD1 aggregates: A potential therapeutic strategy for Amyotrophic lateral sclerosis (ALS)

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-02-28 DOI: 10.1016/j.bbrc.2025.151533

Battur Tserennadmid , Min-Kyung Nam , Ju-Hwang Park , Hyangshuk Rhim , Seongman Kang

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease marked by the accumulation of misfolded Cu/Zn superoxide dismutase (SOD1) protein aggregates in motor neurons, leading to progressive motor dysfunction and ultimately death. While the molecular chaperone heat shock protein 104 (Hsp104) has been shown to reduce protein misfolding by disaggregating protein aggregates, fully degrading these disaggregated proteins remains a significant challenge. In this study, we have investigated the effects of Hsp104 and its hyperactive variant, HAP, in combination with caseinolytic protease P (CIpP), on the disaggregation and degradation of SOD1 aggregates. Using laser confocal microscopy, fluorescence loss in photobleaching (FLIP), and biomolecular fluorescence complementation (BiFC)-fluorescence resonance energy transfer (FRET) assays, we demonstrate that Hsp104 effectively disaggregates SOD1 aggregates across 14 different G93 mutants, classified based on the properties of substituted amino acids, thus restoring protein mobility. Notably, the HAP/CIpP system not only disaggregates ALS-associated SOD1^G93A aggregates but also promotes their proteolytic degradation, as evidenced by a significant reduction in high-order oligomers observed through BiFC and FRET assays. This dual mechanism of action presents.

the HAP/CIpP system holds significant therapeutic potential for ALS and other neurodegenerative diseases characterized by protein aggregates, as it enables both effective disaggregation and degradation of toxic protein aggregates, thereby maintaining protein homeostasis.

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引用次数: 0

A high-fat diet changes the interaction of the extracellular matrix, cytokines, and growth factors in gastric ulcer repair

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-02-28 DOI: 10.1016/j.bbrc.2025.151565

Rie Ohara , Felipe Lima Dario , Maycon Tavares Emílio-Silva , Renata Assunção , Vinícius Peixoto Rodrigues , Gabriela Bueno , Priscila Romano Raimundo , Luis Antonio Justulin , Lúcia Regina Machado da Rocha , Clelia Akiko Hiruma-Lima

Background

Obesity is characterized by persistent low-grade inflammation that alters the gastrointestinal system and healing process. The link between obesity and the prevalence of stomach ulcers has not yet been fully established.

Aims

We investigated the healing features of gastric lesions in male Swiss mice fed a standard diet (SD) or high-fat diet (HFD) using morphometric, biochemical, and molecular parameters.

Methods

After 12 weeks on different diets, the animals underwent acetic acid-induced stomach ulcer surgery. To evaluate healing patterns, the stomachs of the animals were studied at five post-induction times, including the early, middle, and late phases of healing (1, 3, 7, 10, and 14 days). Morphometric features, activity of matrix metalloproteinases 2 and 9 (MMP-2 and 9), and measurement of inflammatory and growth factors were investigated using multiplex immunoassays.

Results

Compared with the SD group, the HFD group demonstrated slowing of the early healing process. During the initial phase of the healing process, the SD group had significantly higher levels of EGF, VEGF-A, and VEGF-D than the HFD group. In the intermediate phase, only the SD group showed a 70 % increase in the regeneration area compared with the initial phase of the procedure. In this phase, the SD group also had higher levels of MMP-9, VEGF-D, and HGF than the HFD group.

Conclusions

HFD can have a negative impact on the healing process of gastric ulcers in animals by delaying repair in gastric tissue when compared with animals consuming SD.

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引用次数: 0

Inhibition of the MLL1-WDR5 interaction modulates epithelial to mesenchymal transition and metabolic pathways in triple-negative breast cancer cells

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-02-28 DOI: 10.1016/j.bbrc.2025.151559

Shilpi Sarkar , Thirukumaran Kandasamy , Siddhartha Sankar Ghosh

Histone methylation is a key epigenetic modulation that regulates gene expression and is often associated with the pathogenesis of various cancers, including triple-negative breast cancer (TNBC). Histone methyltransferase, MLL1-WDR5 complex regulates gene transcription by catalyzing trimethylation of lysine 4 on histone H3 (H3K4me3) and promotes carcinogenesis. Herein, epithelial-to-mesenchymal transition (EMT) in TNBC cells is shown to facilitate upregulation of MLL1 and WDR5 expression by 4.7-fold and 3.84-fold, thereby establishing the association of these proteins in EMT dynamics. Therefore, we explored the therapeutic potential of inhibiting MLL1-WDR5 interaction using the small molecule inhibitor MM-102 in TNBC cell lines. MLL1 inhibition significantly reduced H3K4me3 levels and enhanced the apoptotic population by 30 % in MDA-MB-468 cells, demonstrating its cytotoxic potential. Notably, MM-102 treatment reverses the EMT process by upregulating the expression of epithelial markers (such as E-cadherin and claudin) and downregulating the expression of mesenchymal markers (such as β-catenin, Slug, caveolin 1, and fibronectin). In addition, MLL1 inhibition caused a metabolic shift, with a 5-fold increase in ALDO A and a 4-fold increase in ENO1 expression, indicating enhanced glycolysis. Further reduction in the fatty acid uptake and lipid droplet accumulation by MM-102 treatment signifies that targeting MLL1 also rewires the metabolic network in TNBC cells. Collectively, inhibiting MLL1 represents a promising therapeutic strategy for managing EMT-driven metastasis, reshaping metabolic reprogramming, and ultimately improving therapeutic outcomes in aggressive breast cancer.

组蛋白甲基化是一种调控基因表达的关键表观遗传调控，通常与包括三阴性乳腺癌（TNBC）在内的各种癌症的发病机制有关。组蛋白甲基转移酶、MLL1-WDR5 复合物通过催化组蛋白 H3 上赖氨酸 4 的三甲基化（H3K4me3）来调控基因转录，并促进癌变。在本文中，TNBC 细胞的上皮细胞向间质转化（EMT）过程中，MLL1 和 WDR5 的表达分别上调了 4.7 倍和 3.84 倍，从而确定了这些蛋白在 EMT 动态过程中的关联性。因此，我们在 TNBC 细胞系中使用小分子抑制剂 MM-102 探索了抑制 MLL1-WDR5 相互作用的治疗潜力。在 MDA-MB-468 细胞中，抑制 MLL1 能明显降低 H3K4me3 水平，并使细胞凋亡率提高 30%，这证明了它的细胞毒性潜力。值得注意的是，MM-102 可通过上调上皮标志物（如 E-cadherin 和 claudin）的表达和下调间质标志物（如 β-catenin、Slug、caveolin 1 和 fibronectin）的表达来逆转 EMT 过程。此外，抑制 MLL1 会导致代谢转变，ALDO A 表达增加 5 倍，ENO1 表达增加 4 倍，表明糖酵解增强。MM-102 处理进一步减少了脂肪酸摄取和脂滴积累，这表明靶向 MLL1 还能重构 TNBC 细胞的代谢网络。总而言之，抑制 MLL1 是一种很有前景的治疗策略，可用于控制 EMT 驱动的转移、重塑代谢重编程并最终改善侵袭性乳腺癌的治疗效果。

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引用次数: 0

Intranasal administration of ergothioneine improves memory in a mouse model of multiple system atrophy

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-02-28 DOI: 10.1016/j.bbrc.2025.151550

Kazuto Kimura , Makoto Timon Tanaka , Yasuo Miki , Tomonori Furukawa , Shuya Kasai , Taku Ozaki , Fumiaki Mori , Eri Shibuya , Koichi Wakabayashi

No effective treatments have been established to delay or prevent the progression of multiple system atrophy (MSA), which is characterised by the accumulation of abnormal α-synuclein (α-Syn) species, including toxic α-Syn oligomers, in the central nervous system. In our previous study, we demonstrated that intranasal administration of trehalose reduces the levels of α-Syn oligomer by accelerating their conversion from toxic α-Syn oligomers to less harmful fibrils in a human α-Syn inducible MSA mouse model. This finding suggests that reducing α-Syn oligomers may be a crucial therapeutic strategy for MSA. The present study aimed to assess the potential of intranasal ergothioneine (ERG) administration in ameliorating MSA pathology within the MSA mouse model. A cognitive function test and electrophysiological analysis revealed that ERG administration significantly improved short-term spatial memory associated with hippocampal activity, with performance nearing normal levels. Immunohistochemical analysis showed that ERG treatment increased human α-Syn-positive areas within the dentate gyrus + dentate hilus regions of the hippocampus. By contrast, ERG treatment also led to a reduction in α-Syn phosphorylation in the cerebral cortex. Furthermore, immunoblotting confirmed that ERG treatment elevated expression levels of α-Syn monomer, while significantly reducing α-Syn dimer levels in the ERG-treated MSA model mice compared with untreated counterparts. Thus, the modification of α-Syn induced by ERG treatment may result in a reduction of α-Syn oligomers. Here, we demonstrate that intranasal administration of ERG improved short-term spatial memory in the MSA mouse model.

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引用次数: 0

Structural analysis of substrate recognition loop flexibility in D-arabinose dehydrogenase from Candida auris

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-02-28 DOI: 10.1016/j.bbrc.2025.151573

Meng Dan , Zhang Jie , Bai Xue , Ki Hyun Nam , Xu Yongbin

Candida auris is an emerging fungal pathogen that poses a significant threat to global health due to its multidrug resistance and ability to persist in healthcare settings. A key factor contributing to its survival and virulence is its capacity to combat oxidative stress, a process primarily driven by oxidative stress-related enzymes. One such enzyme, d-arabinose dehydrogenase from C. auris (CaAldO), plays a crucial role in the biosynthesis of d-erythroascorbic acid (EASC), an essential antioxidant that shields fungal cells from oxidative damage. CaAldO catalyzes the oxidation of d-arabinose to D-arabinono-1,5-lactone, a key precursor in EASC synthesis, thereby enhancing the oxidative stress resistance of C. auris. To elucidate its structural features, we determined the high-resolution crystal structure of CaAldO at 1.95 Å. Its cofactor-binding pocket is formed by four loop regions within the TIM-barrel fold. Notably, Loops A and C in the substrate-binding pocket exhibit significant flexibility, facilitating the transition between the open and closed conformations of the cofactor-binding pocket of CaAldO. A structural comparison of CaAldO with its homolog ScAra1 revealed notable differences in the length and conformation of the substrate recognition loops, as well as variations in the cofactor-binding pocket. These findings enhance our understanding of the unique structural properties of CaAldO and offer insights into developing novel antifungal strategies targeting C. auris.

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引用次数: 0

Divergent roles of 25-hydroxyvitamin D3 and 1α,25-dihydroxyvitamin D3 in neural fate determination: A CYP27B1-dependent neuron formation and VDR-dependent astrocyte development

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-02-28 DOI: 10.1016/j.bbrc.2025.151547

Shusaku Kimura , Shintaro Tagami , Hiroki Mano , Atsushi Kittaka , Yuka Ida , Yuta Takagi , Kurumi Nakagawa , Tasuku Arai , Satoshi Yokota , Naoko Tsugawa , Maya Kamao , Yoshitomo Suhara , Toshiyuki Sakaki , Kimie Nakagawa , Toshio Okano , Yoshihisa Hirota

Vitamin D plays a crucial role in neural differentiation, yet its precise mechanisms remain unclear. In this study, we investigated the effects of vitamin D metabolites, 25-hydroxyvitamin D₃ (25D₃) and 1α,25-dihydroxyvitamin D₃ (1α,25D₃), on neural differentiation using Cyp27b1^−/− and Vdr^−/− knockout mice-derived neural stem cells. We found that 1α,25D₃ promotes neuronal differentiation via vitamin D receptor (VDR), whereas some of its effects occur independently of VDR. Additionally, 25D₃ requires conversion to 1α,25D₃ by CYP27B1 to induce neuronal differentiation. In contrast, both 25D₃ and 1α,25D₃ promoted astrocyte differentiation regardless of CYP27B1 expression but required VDR. Furthermore, using vitamin D derivatives, we demonstrated that VDR binding affinity does not directly correlate with neurogenic potential. These findings reveal distinct VDR-dependent and VDR-independent pathways in neural differentiation, highlighting a previously unrecognized role of vitamin D metabolism in neural fate determination.

{"title":"Divergent roles of 25-hydroxyvitamin D3 and 1α,25-dihydroxyvitamin D3 in neural fate determination: A CYP27B1-dependent neuron formation and VDR-dependent astrocyte development","authors":"Shusaku Kimura , Shintaro Tagami , Hiroki Mano , Atsushi Kittaka , Yuka Ida , Yuta Takagi , Kurumi Nakagawa , Tasuku Arai , Satoshi Yokota , Naoko Tsugawa , Maya Kamao , Yoshitomo Suhara , Toshiyuki Sakaki , Kimie Nakagawa , Toshio Okano , Yoshihisa Hirota","doi":"10.1016/j.bbrc.2025.151547","DOIUrl":"10.1016/j.bbrc.2025.151547","url":null,"abstract":"<div><div>Vitamin D plays a crucial role in neural differentiation, yet its precise mechanisms remain unclear. In this study, we investigated the effects of vitamin D metabolites, 25-hydroxyvitamin D<sub>3</sub> (25D<sub>3</sub>) and 1α,25-dihydroxyvitamin D<sub>3</sub> (1α,25D<sub>3</sub>), on neural differentiation using <em>Cyp27b1</em><sup>−/−</sup> and <em>Vdr</em><sup>−/−</sup> knockout mice-derived neural stem cells. We found that 1α,25D<sub>3</sub> promotes neuronal differentiation via vitamin D receptor (VDR), whereas some of its effects occur independently of VDR. Additionally, 25D<sub>3</sub> requires conversion to 1α,25D<sub>3</sub> by CYP27B1 to induce neuronal differentiation. In contrast, both 25D<sub>3</sub> and 1α,25D<sub>3</sub> promoted astrocyte differentiation regardless of CYP27B1 expression but required VDR. Furthermore, using vitamin D derivatives, we demonstrated that VDR binding affinity does not directly correlate with neurogenic potential. These findings reveal distinct VDR-dependent and VDR-independent pathways in neural differentiation, highlighting a previously unrecognized role of vitamin D metabolism in neural fate determination.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"755 ","pages":"Article 151547"},"PeriodicalIF":2.5,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143550134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Anti-transferrin receptor antibody (JST-TFR09/PPMX-T003) induces ferroptosis in adult T-cell leukemia/lymphoma (ATLL) cells

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-02-28 DOI: 10.1016/j.bbrc.2025.151564

Yanuar Rahmat Fauzi , Shingo Nakahata , Kazuya Shimoda , Tadashi Matsuura , Shinji Hagiwara , Kentaro Inoue , Hiroshi Moritake , Kazuhiro Morishita

Previously, we developed a complete human IgG TFR1 antibody (JST-TFR09/PPMX-T003) that showed a potentially practical therapeutic effect against adult T-cell leukemia/lymphoma (ATLL) in vitro and in vivo. In the present study, to elucidate the molecular mechanism underlying ATLL cell death induced by anti-TFR1 antibodies, we performed comprehensive gene expression analysis and mass spectrometry on ATLL cells treated with PPMX-T003 antibody. These results suggest that PPMX-T003 antibody treatment of ATLL cell lines induces ferroptosis mediated by ferritin degradation. PPMX-T003 antibody-treated ATLL cell lines showed a decrease in ferritin proteins, an increase in ferrous iron (Fe²⁺), reactive oxygen species (ROS) generation, and malondialdehyde as induction of lipid peroxidation. Moreover, treatment with a ferroptosis inhibitor (ferroportin-1) inhibited the cell death induced by PPMX-T003 antibody in ATLL cells. Furthermore, NCO4A and LC3-II were induced following antibody treatment, and ferritin degradation was inhibited by lysosomal inhibitors, suggesting that ferritin degradation depends on autolysosomal system activation. Here, we introduce ferroptosis as one of the potential mechanisms of PPMX-T003 antibody, which is promising for future therapeutic antibodies targeting a wide range of leukemia and cancers, including ATLL.

{"title":"Anti-transferrin receptor antibody (JST-TFR09/PPMX-T003) induces ferroptosis in adult T-cell leukemia/lymphoma (ATLL) cells","authors":"Yanuar Rahmat Fauzi , Shingo Nakahata , Kazuya Shimoda , Tadashi Matsuura , Shinji Hagiwara , Kentaro Inoue , Hiroshi Moritake , Kazuhiro Morishita","doi":"10.1016/j.bbrc.2025.151564","DOIUrl":"10.1016/j.bbrc.2025.151564","url":null,"abstract":"<div><div>Previously, we developed a complete human IgG TFR1 antibody (JST-TFR09/PPMX-T003) that showed a potentially practical therapeutic effect against adult T-cell leukemia/lymphoma (ATLL) in vitro and in vivo. In the present study, to elucidate the molecular mechanism underlying ATLL cell death induced by anti-TFR1 antibodies, we performed comprehensive gene expression analysis and mass spectrometry on ATLL cells treated with PPMX-T003 antibody. These results suggest that PPMX-T003 antibody treatment of ATLL cell lines induces ferroptosis mediated by ferritin degradation. PPMX-T003 antibody-treated ATLL cell lines showed a decrease in ferritin proteins, an increase in ferrous iron (Fe<sup>2+</sup>), reactive oxygen species (ROS) generation, and malondialdehyde as induction of lipid peroxidation. Moreover, treatment with a ferroptosis inhibitor (ferroportin-1) inhibited the cell death induced by PPMX-T003 antibody in ATLL cells. Furthermore, NCO4A and LC3-II were induced following antibody treatment, and ferritin degradation was inhibited by lysosomal inhibitors, suggesting that ferritin degradation depends on autolysosomal system activation. Here, we introduce ferroptosis as one of the potential mechanisms of PPMX-T003 antibody, which is promising for future therapeutic antibodies targeting a wide range of leukemia and cancers, including ATLL.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"756 ","pages":"Article 151564"},"PeriodicalIF":2.5,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143611466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cortical perforation promotes bone regeneration by enhancing nerve growth factor secretion

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-02-28 DOI: 10.1016/j.bbrc.2025.151562

Yao Jiao , Yitong Liu , Xiaoyan Li , Nannan Han , Siyan Liu , Juan Du , Junji Xu , Song Li , Lijia Guo , Yi Liu

Adequate blood supply around bone grafts is crucial in periodontal regenerative surgery. Research suggests that cortical perforation during surgery can stimulate angiogenesis and cell migration, increase blood supply to the surgical site, and promote local tissue regeneration. However, the effects of perforation on the local tissue microenvironment and the molecular mechanisms by which corticotomy promotes bone regeneration remain unclear. In this study, a rat model was established to investigate the effect of cortical perforation on osteogenesis around bone grafts. Different groups of alveolar bone were ground to prepare conditioned medium, and the effect on osteogenic differentiation of periodontal ligament stem cells (PDLSCs) was observed in vitro. Finally, we focused on the nerve growth factor (NGF) with the most obvious difference and verified the role of NGF and its potential molecular mechanism in vivo and in vitro. The results showed that osteogenesis around the local bone graft was more pronounced after corticotomy. Additionally, using a tissue-conditioned medium promoted the osteogenic differentiation of PDLSCs, while the expression of NGF increased locally after corticotomy. Further investigation using exogenous NGF or NGF inhibitors confirmed that NGF plays a crucial role in promoting osteogenesis around the bone graft, specifically through activating the JNK/c-Jun pathway. These findings suggest that targeting the mechanism by which cortical perforation promotes bone regeneration could lead to new therapeutic strategies for enhancing bone augmentation in regenerative surgery.

{"title":"Cortical perforation promotes bone regeneration by enhancing nerve growth factor secretion","authors":"Yao Jiao , Yitong Liu , Xiaoyan Li , Nannan Han , Siyan Liu , Juan Du , Junji Xu , Song Li , Lijia Guo , Yi Liu","doi":"10.1016/j.bbrc.2025.151562","DOIUrl":"10.1016/j.bbrc.2025.151562","url":null,"abstract":"<div><div>Adequate blood supply around bone grafts is crucial in periodontal regenerative surgery. Research suggests that cortical perforation during surgery can stimulate angiogenesis and cell migration, increase blood supply to the surgical site, and promote local tissue regeneration. However, the effects of perforation on the local tissue microenvironment and the molecular mechanisms by which corticotomy promotes bone regeneration remain unclear. In this study, a rat model was established to investigate the effect of cortical perforation on osteogenesis around bone grafts. Different groups of alveolar bone were ground to prepare conditioned medium, and the effect on osteogenic differentiation of periodontal ligament stem cells (PDLSCs) was observed <em>in vitro</em>. Finally, we focused on the nerve growth factor (NGF) with the most obvious difference and verified the role of NGF and its potential molecular mechanism <em>in vivo</em> and <em>in vitro</em>. The results showed that osteogenesis around the local bone graft was more pronounced after corticotomy. Additionally, using a tissue-conditioned medium promoted the osteogenic differentiation of PDLSCs, while the expression of NGF increased locally after corticotomy. Further investigation using exogenous NGF or NGF inhibitors confirmed that NGF plays a crucial role in promoting osteogenesis around the bone graft, specifically through activating the JNK/c-Jun pathway. These findings suggest that targeting the mechanism by which cortical perforation promotes bone regeneration could lead to new therapeutic strategies for enhancing bone augmentation in regenerative surgery.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"755 ","pages":"Article 151562"},"PeriodicalIF":2.5,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143534646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

TRPC1 downregulation enhances catecholamine secretion in adrenal chromaffin cells under metabolic syndrome conditions

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-02-28 DOI: 10.1016/j.bbrc.2025.151566

Ying Hao , Weiheng Zhang , Mengying Sun , Kun Lan , Ningning Yang , Shangze Yang , Xingjuan Chen

Increased catecholamine (CA) secretion from the adrenal medulla has been observed in patients with Metabolic Syndrome (MetS) and in animal models. Neuroendocrine adrenal medulla chromaffin cells (AMCCs) release catecholamines in response to Ca²⁺ influx through calcium channels. This study investigates the role of TRPC channels in mediating calcium influx in AMCCs under MetS conditions. NGF-induced PC12 cells were cultured in a MetS-mimicking (MMetS) medium, and CA secretion, as well as TRPC1 and TRPC5 expression, were assessed. The role of TRPC1 was further explored using siRNA-mediated knockdown in PC12 cells. Additionally, wild-type (WT) and TRPC1 knockout (TRPC1^−/−) mice on a high-fat diet (HFD) were used to evaluate in vivo CA secretion and TRPC channel expression. Intracellular [Ca²⁺] levels in isolated chromaffin cells from mice were measured using live-cell imaging. CA secretion was significantly increased in PC12 cells cultured in the MMetS medium, which was accompanied by downregulation of TRPC1 and upregulation of TRPC5. TRPC1 knockdown via siRNA further increased TRPC5 mRNA levels and CA secretion in MMetS-treated PC12 cells. In MetS mice, TRPC1 deletion led to enhanced CA secretion, elevated body weight, cholesterol levels, and blood pressure compared to WT mice. TRPC1 deletion also potentiated TRPC-mediated calcium influx in chromaffin cells and further upregulated TRPC5 expression under MetS conditions. These findings suggest that TRPC1 downregulation enhances intracellular calcium signaling and CA secretion by reducing its inhibitory effect on TRPC5, providing insights for potential therapeutic strategies in MetS-related pathophysiology.

{"title":"TRPC1 downregulation enhances catecholamine secretion in adrenal chromaffin cells under metabolic syndrome conditions","authors":"Ying Hao , Weiheng Zhang , Mengying Sun , Kun Lan , Ningning Yang , Shangze Yang , Xingjuan Chen","doi":"10.1016/j.bbrc.2025.151566","DOIUrl":"10.1016/j.bbrc.2025.151566","url":null,"abstract":"<div><div>Increased catecholamine (CA) secretion from the adrenal medulla has been observed in patients with Metabolic Syndrome (MetS) and in animal models. Neuroendocrine adrenal medulla chromaffin cells (AMCCs) release catecholamines in response to Ca<sup>2+</sup> influx through calcium channels. This study investigates the role of TRPC channels in mediating calcium influx in AMCCs under MetS conditions. NGF-induced PC12 cells were cultured in a MetS-mimicking (MMetS) medium, and CA secretion, as well as TRPC1 and TRPC5 expression, were assessed. The role of TRPC1 was further explored using siRNA-mediated knockdown in PC12 cells. Additionally, wild-type (WT) and TRPC1 knockout (<em>TRPC1</em><sup>−/−</sup>) mice on a high-fat diet (HFD) were used to evaluate in vivo CA secretion and TRPC channel expression. Intracellular [Ca<sup>2+</sup>] levels in isolated chromaffin cells from mice were measured using live-cell imaging. CA secretion was significantly increased in PC12 cells cultured in the MMetS medium, which was accompanied by downregulation of TRPC1 and upregulation of TRPC5. TRPC1 knockdown via siRNA further increased TRPC5 mRNA levels and CA secretion in MMetS-treated PC12 cells. In MetS mice, TRPC1 deletion led to enhanced CA secretion, elevated body weight, cholesterol levels, and blood pressure compared to WT mice. TRPC1 deletion also potentiated TRPC-mediated calcium influx in chromaffin cells and further upregulated TRPC5 expression under MetS conditions. These findings suggest that TRPC1 downregulation enhances intracellular calcium signaling and CA secretion by reducing its inhibitory effect on TRPC5, providing insights for potential therapeutic strategies in MetS-related pathophysiology.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"755 ","pages":"Article 151566"},"PeriodicalIF":2.5,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143550133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Myricetin supresses HBV replication both in vitro and in vivo via inhibition of HBV promoter SP2

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-02-28 DOI: 10.1016/j.bbrc.2025.151560

LiLi Lu , Duo Cai , JiangNan Wang , Wei Li , XiLin Zhu , Ying Liu , ZhenHui Xin , ShiHai Liu , XiaoPan Wu

Hepatitis B virus (HBV) infection remains a significant global public health concern. Myricetin, a flavonoid compound widely distributed in natural plants, has demonstrated multiple biological functions in combating diseases such as cancer and inflammation. In this research, we explored the mechanism of myricetin against HBV replication. We employed various experiments such as ELISA, Southern Blot, Northern Blot, Western Blot, RT-qPCR, Dual luciferase reporter gene assay, ChIP, EMSA, IHC, Immunofluorescence, AAV infection, and isolation of primary human hepatocytes (PHH) in this study. Our results showed that myricetin significantly reduced the expression of HBV markers, including HBsAg, HBeAg and covalently closed circular DNA (cccDNA), in HepG2-NTCP cells and PHH. We further confirmed these findings using AAV-HBV cell and mouse models. Furthermore, we found that myricetin significantly downregulated HBV SP2 promoter activity. Mechanistically, myricetin reduced CEBPA expression, which in turn interfered with the binding of CEBPA to the HBV SP2 promoter, leading to an antiviral effect. In conclusion, myricetin exhibited promising antiviral activity against HBV, suggesting its potential for novel HBV treatment.

{"title":"Myricetin supresses HBV replication both in vitro and in vivo via inhibition of HBV promoter SP2","authors":"LiLi Lu , Duo Cai , JiangNan Wang , Wei Li , XiLin Zhu , Ying Liu , ZhenHui Xin , ShiHai Liu , XiaoPan Wu","doi":"10.1016/j.bbrc.2025.151560","DOIUrl":"10.1016/j.bbrc.2025.151560","url":null,"abstract":"<div><div>Hepatitis B virus (HBV) infection remains a significant global public health concern. Myricetin, a flavonoid compound widely distributed in natural plants, has demonstrated multiple biological functions in combating diseases such as cancer and inflammation. In this research, we explored the mechanism of myricetin against HBV replication. We employed various experiments such as ELISA, Southern Blot, Northern Blot, Western Blot, RT-qPCR, Dual luciferase reporter gene assay, ChIP, EMSA, IHC, Immunofluorescence, AAV infection, and isolation of primary human hepatocytes (PHH) in this study. Our results showed that myricetin significantly reduced the expression of HBV markers, including HBsAg, HBeAg and covalently closed circular DNA (cccDNA), in HepG2-NTCP cells and PHH. We further confirmed these findings using AAV-HBV cell and mouse models. Furthermore, we found that myricetin significantly downregulated HBV SP2 promoter activity. Mechanistically, myricetin reduced CEBPA expression, which in turn interfered with the binding of CEBPA to the HBV SP2 promoter, leading to an antiviral effect. In conclusion, myricetin exhibited promising antiviral activity against HBV, suggesting its potential for novel HBV treatment.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"755 ","pages":"Article 151560"},"PeriodicalIF":2.5,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143550140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0