International Journal of Biochemistry & Cell Biology最新文献

英文中文

Integrated stress response-upregulated mitochondrial SLC1A5var enhances glucose dependency in human breast cancer cells in vitro. 综合应激反应上调线粒体 SLC1A5var 可增强体外人类乳腺癌细胞对葡萄糖的依赖性。

IF 3.4 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

International Journal of Biochemistry & Cell Biology

Pub Date : 2024-11-04 DOI: 10.1016/j.biocel.2024.106688

Sheng-Fan Wang, Yu-Chieh Ho, Chian-Ying Chou, Yuh-Lih Chang, Hsin-Chen Lee, Ling-Ming Tseng

Breast cancer is the most commonly diagnosed cancer among women. The growth of triple-negative breast cancer (TNBC) cells is glucose-dependent. The integrated stress response (ISR) is a cellular stress response to glucose depletion. The ISR-solute carrier family 7 member 11 pathway is activated during glucose depletion and contributes to glucose dependence by decreasing intracellular glutamate levels. Solute carrier family 1 member 5 (SLC1A5) and the mitochondrial solute carrier family 1 member 5 variant (SLC1A5var) are glutamine transporters that play essential roles in the reprogramming of cancer metabolism. However, whether ISR can regulate mitochondrial SLC1A5var expression and further affect glucose dependence remains unclear. Glucose depletion-, oligomycin-, and salubrinal-activated activating transcription factor-4 (ATF4) induced SLC1A5var expression. ATF4 is critical for SLC1A5var regulation, as it binds to specific regulatory elements in its promoter. SLC1A5var knockdown decreases glucose depletion-induced cell death, whereas SLC1A5var overexpression increases glucose depletion-induced cell death in TNBC cells. SLC1A5var knockdown reduced cancer cell proliferation, colony formation, and migration, whereas SLC1A5var overexpression increased cell proliferation and migration. Moreover, the knockdown of SLC1A5var reduces the oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) while increasing the maximal OCR and ECAR under glucose depletion. These results suggest that activated ISR-induced increased expression of SLC1A5var may regulate mitochondrial oxidative phosphorylation and glycolytic metabolic characteristics to enhance glucose depletion-induced cell death. In conclusion, SLC1A5var plays a vital role in metabolic reprogramming and may be a potential target for breast cancer treatment.

乳腺癌是女性中最常见的癌症。三阴性乳腺癌（TNBC）细胞的生长依赖于葡萄糖。综合应激反应（ISR）是细胞对葡萄糖耗竭的应激反应。在葡萄糖耗竭时，ISR-溶质运载家族 7 成员 11 通路被激活，并通过降低细胞内谷氨酸水平来促进葡萄糖依赖性。溶质运载家族 1 成员 5（SLC1A5）和线粒体溶质运载家族 1 成员 5 变体（SLC1A5var）是谷氨酰胺转运体，在癌症代谢重编程中发挥着重要作用。然而，ISR 是否能调节线粒体 SLC1A5var 的表达并进一步影响葡萄糖依赖性仍不清楚。葡萄糖耗竭、低聚霉素和柳氮磺胺吡啶激活的活化转录因子-4（ATF4）诱导了SLC1A5var的表达。ATF4 与 SLC1A5var 启动子中的特定调控元件结合，因此对 SLC1A5var 的调控至关重要。在 TNBC 细胞中，SLC1A5var 敲除会减少葡萄糖耗竭诱导的细胞死亡，而 SLC1A5var 过表达则会增加葡萄糖耗竭诱导的细胞死亡。SLC1A5var 敲除会减少癌细胞的增殖、集落形成和迁移，而 SLC1A5var 过表达则会增加细胞的增殖和迁移。此外，敲除 SLC1A5var 会降低耗氧率（OCR）和细胞外酸化率（ECAR），同时增加葡萄糖耗竭下的最大耗氧率和细胞外酸化率。这些结果表明，活化的 ISR 诱导的 SLC1A5var 表达增加可能会调节线粒体氧化磷酸化和糖酵解代谢特性，从而增强葡萄糖耗竭诱导的细胞死亡。总之，SLC1A5var 在代谢重编程中发挥着重要作用，可能是乳腺癌治疗的潜在靶点。

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引用次数: 0

Corrigendum to “Dual blockade of the A1 and A2A adenosine receptor prevents amyloid beta toxicity in neuroblastoma cells exposed to aluminum chloride” [Int. J. Biochem. Cell Biol. 54 (2014) 122–136] 更正："双重阻断A1和A2A腺苷受体可防止暴露于氯化铝的神经母细胞瘤细胞中淀粉样β的毒性" [Int. J. Biochem. Cell Biol. 54 (2014) 122-136]。

IF 3.4 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

International Journal of Biochemistry & Cell Biology

Pub Date : 2024-11-01 DOI: 10.1016/j.biocel.2024.106677

Salvatore Giunta , Violetta Andriolo , Alessandro Castorina

引用次数: 0

Corrigendum to “15-lipoxygenase-1/15-hydroxyeicosatetraenoic acid promotes hepatocellular cancer cells growth through protein kinase B and heat shock protein 90 complex activation” [Int. J. Biochem. Cell Biol. 45 (2013) 1031–41] 更正："15-脂氧合酶-1/15-羟基二十碳四烯酸通过蛋白激酶 B 和热休克蛋白 90 复合物激活促进肝癌细胞生长" [Int. J. Biochem. Cell Biol. 45 (2013) 1031-41]。

IF 3.4 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

International Journal of Biochemistry & Cell Biology

Pub Date : 2024-11-01 DOI: 10.1016/j.biocel.2024.106670

Jun Ma , Lei Zhang , Jianguo Zhang , Mengmeng Liu , Liuping Wei , Tingting Shen , Cui Ma , Yanyan Wang , Yingli Chen , Daling Zhu

引用次数: 0

Retraction notice to “Downregulation of Rab23 inhibits proliferation, invasion, and metastasis of human ovarian cancer” [Int. J. Biochem. Cell Biol. 116 (2019) 105617] 下调 Rab23 抑制人类卵巢癌的增殖、侵袭和转移》的撤稿通知 [Int. J. Biochem. Cell Biol. 116 (2019) 105617]。

IF 3.4 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

International Journal of Biochemistry & Cell Biology

Pub Date : 2024-11-01 DOI: 10.1016/j.biocel.2024.106673

Lingling Gao , Mingjun Zheng , Qian Guo , Xin Nie , Xiao Li , Yingying Hao , Juanjuan Liu , Liancheng Zhu , Bei Lin

引用次数: 0

Retraction notice to “Nucleocapsid protein of SARS-CoV activates the expression of cyclooxygenase-2 by binding directly to regulatory elements for nuclear factor-kappa B and CCAAT/enhancer binding protein” [Int. J. Biochem. Cell Biol. 38 (2006) 1417–1428] 关于 "SARS-CoV的核壳蛋白通过直接与核因子-卡巴B和CCAAT/增强子结合蛋白的调控元件结合，激活环氧化酶-2的表达 "的撤稿通知[Int. J. Biochem. Cell Biol. 38 (2006) 1417-1428]。

IF 3.4 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

International Journal of Biochemistry & Cell Biology

Pub Date : 2024-11-01 DOI: 10.1016/j.biocel.2024.106674

Xiaohong Yan, Qian Hao, Yongxin Mu, Khalid Amine Timani, Linbai Ye, Ying Zhu, Jianguo Wu

引用次数: 0

Aminoadipic acid aggravates atherosclerotic vascular inflammation through ROS/TXNIP/NLRP3 pathway, a harmful microbial metabolite reduced by paeonol 氨基己二酸通过 ROS/TXNIP/NLRP3 通路加重动脉粥样硬化性血管炎症，芍药酚可减少有害微生物代谢物的产生

IF 3.4 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

International Journal of Biochemistry & Cell Biology

Pub Date : 2024-10-26 DOI: 10.1016/j.biocel.2024.106678

Tian Wang , Hongfei Wu , Xiaoyan Shi , Min Dai , Yarong Liu

Aim

Our previous study has found a differential microbial metabolite in atherosclerosis (AS) mice, aminoadipic acid (AAA), which was considered as a potential harmful metabolite. However, whether it can promote AS vascular inflammation and its mechanisms remain unclear. Paeonol (Pae) plays an anti-AS role by regulating the metabolic profile, but whether Pae exerts its antiatherogenic effect by reducing serum AAA levels is unknown.

Results

The clinical trial results showed that the AS patients’ serum AAA levels were higher than those healthy people’. Besides, AAA supplementation could increase aortic plaque size, serum inflammatory cytokines levels and liver malondialdehyde, superoxide dismutase levels in AS mice. Moreover, after AAA stimulation, the ROS levels and ASC, TXNIP, NLRP3 and caspase-1 proteins levels were increased in HUVECs, which could be reversed by antioxidant NAC and NLRP3 inhibitor. Pae significantly reduced the plaque size in the aorta, improved blood lipid levels and decreased serum inflammation factor levels in AS mice. Simultaneously, Pae could reduce the serum AAA levels of AS mice through the gut microbiota transmission. Finally, Pae inhibited NLRP3 inflammasome activation in aortas of AS mice. Broad-spectrum antibiotics could weaken the inhibitory effect of Pae on NLRP3 inflammasome.

Conclusion

Our study clarified that AAA could promote AS vascular inflammation via activating the ROS/TXNIP/NLRP3 pathway. Pae could inhibit AS development by reducing serum AAA levels in a microbiota-dependent manner. Taken together, we proposed that AAA could be served as a potential biomarker for AS clinical diagnosis and provided a new treatment strategy for AS.

目的我们之前的研究在动脉粥样硬化（AS）小鼠体内发现了一种不同的微生物代谢物--氨基己二酸（AAA），它被认为是一种潜在的有害代谢物。然而，它是否能促进动脉粥样硬化血管炎症及其机制仍不清楚。芍药酚（Pae）通过调节代谢轮廓发挥抗强直性脊柱炎的作用，但芍药酚是否通过降低血清 AAA 水平来发挥抗动脉粥样硬化的作用尚不清楚。此外，补充 AAA 可增加 AS 小鼠主动脉斑块的大小、血清炎性细胞因子水平和肝脏丙二醛、超氧化物歧化酶水平。此外，AAA刺激后，HUVECs中ROS水平、ASC、TXNIP、NLRP3和caspase-1蛋白水平均升高，而抗氧化剂NAC和NLRP3抑制剂可逆转这一现象。Pae能明显缩小AS小鼠主动脉斑块的大小，改善血脂水平，降低血清炎症因子水平。同时，Pae 还能通过肠道微生物群传递降低 AS 小鼠血清 AAA 水平。最后，Pae能抑制AS小鼠主动脉中NLRP3炎性体的激活。结论我们的研究阐明了AAA可通过激活ROS/TXNIP/NLRP3途径促进AS血管炎症。Pae可通过降低血清中的AAA水平，以微生物群依赖的方式抑制强直性脊柱炎的发展。综上所述，我们认为AAA可作为强直性脊柱炎临床诊断的潜在生物标志物，并为强直性脊柱炎提供了一种新的治疗策略。

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引用次数: 0

The emerging role of Never-in-Mitosis A - Related Kinases in the endothelium 内皮细胞中从未蜕变的 A 相关激酶的新作用

IF 3.4 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

International Journal of Biochemistry & Cell Biology

Pub Date : 2024-10-24 DOI: 10.1016/j.biocel.2024.106679

Nektarios Barabutis, Saikat Fakir

The endothelium forms a monolayer, which functions to ensure tissue homeostasis. Barrier hyperpermeability has been associated with lung, brain and eye disease. An emerging body of evidence reports the involvement of Never-in-Mitosis A - Related Kinases in vascular responses, suggesting their value as potential therapeutic targets in endothelial-dependent disorders.

内皮形成一个单层，具有确保组织稳态的功能。屏障高渗透性与肺、脑和眼部疾病有关。越来越多的证据表明，与内皮细胞有关的 A 型激酶参与了血管反应，这表明它们作为内皮依赖性疾病的潜在治疗靶点具有潜在价值。

引用次数: 0

ASPSCR1::TFE3-mediated upregulation of insulin receptor substrate 2 (IRS-2) activates PI3K/AKT signaling and promotes malignant phenotype ASPSCR1::TFE3介导的胰岛素受体底物2（IRS-2）上调激活了PI3K/AKT信号转导，并促进了恶性表型的形成。

IF 3.4 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

International Journal of Biochemistry & Cell Biology

Pub Date : 2024-10-16 DOI: 10.1016/j.biocel.2024.106676

Naoko Ishiguro, Mayumi Nakagawa

The ASPSCR1::TFE3 fusion gene, resulting from chromosomal translocation, is detected in alveolar soft part sarcoma (ASPS) and a subset of renal cell carcinomas (RCC). The ASPSCR1::TFE3 oncoprotein, functioning as an aberrant transcription factor, contributes to tumor development and progression by inappropriately upregulating target genes. Here, we identified insulin receptor substrate 2 (IRS-2), a cytoplasmic adaptor protein, as a novel transcriptional target of ASPSCR1::TFE3. Ectopic expression of ASPSCR1::TFE3 led to increased IRS-2 mRNA and protein levels. Chromatin immunoprecipitation and luciferase assays demonstrated that ASPSCR1::TFE3 bound to the IRS-2 promoter region and enhanced its transcription. Moreover, IRS-2 was highly expressed in the ASPSCR1::TFE3-positive RCC cell line FU-UR1, while small interfering RNA-mediated depletion of ASPSCR1::TFE3 markedly decreased IRS-2 mRNA and protein levels. Functionally, IRS-2 knockdown attenuated activation of the PI3K/AKT pathway and reduced proliferation, migration, invasion, adhesion, and clonogenicity in FU-UR1 cells. Pharmacological inhibition of IRS-2 also reduced AKT activation as well as cell viability, clonogenicity, migration, invasion, and adhesion. These findings suggest that IRS-2, regulated by ASPSCR1::TFE3, promotes tumor progression by activating PI3K/AKT signaling and enhancing the malignant phenotype.

在肺泡软组织肉瘤（ASPS）和部分肾细胞癌（RCC）中发现了染色体易位产生的 ASPSCR1::TFE3 融合基因。ASPSCR1::TFE3肿瘤蛋白作为一种异常转录因子，通过不适当地上调靶基因来促进肿瘤的发生和发展。在这里，我们发现细胞质适配蛋白胰岛素受体底物2（IRS-2）是ASPSCR1::TFE3的一个新的转录靶标。异位表达ASPSCR1::TFE3导致IRS-2 mRNA和蛋白水平升高。染色质免疫共沉淀和荧光素酶试验证明，ASPSCR1::TFE3与IRS-2启动子区域结合并增强了其转录。此外，IRS-2在ASPSCR1::TFE3阳性的RCC细胞系FU-UR1中高表达，而小干扰RNA介导的ASPSCR1::TFE3去除可显著降低IRS-2 mRNA和蛋白水平。在功能上，IRS-2敲除可减轻PI3K/AKT通路的激活，降低FU-UR1细胞的增殖、迁移、侵袭、粘附和克隆性。药理抑制 IRS-2 也会降低 AKT 的活化以及细胞活力、迁移、侵袭和粘附性。这些发现表明，IRS-2受ASPSCR1::TFE3调控，通过激活PI3K/AKT信号和增强恶性表型促进肿瘤进展。

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引用次数: 0

Paeoniflorin regulates microglia-astrocyte crosstalk, inhibits inflammatory response, and alleviates neuropathic pain through HSP90AA1/HMGB1 signaling pathway 芍药苷可通过HSP90AA1/HMGB1信号通路调节小胶质细胞与星形胶质细胞之间的串扰、抑制炎症反应并缓解神经性疼痛。

IF 3.4 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

International Journal of Biochemistry & Cell Biology

Pub Date : 2024-10-11 DOI: 10.1016/j.biocel.2024.106675

Fengqin Luo , Juan Zhang , Yunfei Miao , Danhong Wu , Hongxia Shen , Man Lu

Given the unclear, complex pathogenesis of neuropathic pain and the potential of paeoniflorin in relieving neuropathic pain, this study aimed to further clarify the therapeutic effect of paeoniflorin on neuropathic pain and to preliminarily explore the possible protective mechanisms of paeoniflorin. Chronic constrictive injury-induced Sprague Dawley rats and lipopolysaccharide-induced BV-2 cells were used for in vivo and in vitro experiments, respectively. The exosome uptake assay of mouse astrocytes (PKH-67 fluorescent labeling) and the mechanical nociceptive assay (the von Frey fibrous filaments) were performed. The effects of paeoniflorin and its downstream mechanisms on microglial and astrocyte activation, inflammation-associated proteins and exosome marker were determined. Paeoniflorin alleviated mechanical abnormal pain, decreased levels of ionized calcium binding adapter molecule-1 (Iba-1), glial fibrillary acidic protein, Heat Shock Protein 90 Alpha Family Class A Member 1 (HSP90AA1, inflammatory factor) and High Mobility Group Box 1 (HMGB1, inflammation-related protein), and inhibited neuronal apoptosis in chronic constrictive injury rats or lipopolysaccharide-induced BV-2 cells. However, these effects were offset by HSP90AA1 overexpression in lipopolysaccharide-induced BV-2 cells. Exosomes of BV-2 cells could be absorbed by mouse astrocytes. In addition, HSP90AA1 overexpression reversed the effects of paeoniflorin on HMGB1 expression and inflammatory factors and proteins in mouse astrocytes co-cultured with exosome. Collectively, paeoniflorin alleviates neuropathic pain and inhibits inflammatory responses in chronic constrictive injury by modulating microglia-astrocyte crosstalk through HSP90AA1/HMGB1 pathways, which further evidences the potential of paeoniflorin in the treatment of neuropathic pain.

鉴于神经病理性疼痛的发病机制不明确且复杂，以及芍药苷在缓解神经病理性疼痛方面的潜力，本研究旨在进一步阐明芍药苷对神经病理性疼痛的治疗作用，并初步探讨芍药苷可能的保护机制。实验分别采用慢性收缩性损伤诱导的 Sprague Dawley 大鼠和脂多糖诱导的 BV-2 细胞进行体内和体外实验。进行了小鼠星形胶质细胞外泌体摄取试验（PKH-67荧光标记）和机械痛觉试验（von Frey纤维丝）。测定了芍药苷及其下游机制对小胶质细胞和星形胶质细胞活化、炎症相关蛋白和外泌体标记物的影响。芍药苷减轻了机械性异常疼痛，降低了离子化钙结合适配分子-1（Iba-1）、神经胶质纤维酸性蛋白、热休克蛋白 90 Alpha 家族 A 类成员 1（HSP90AA1，炎症因子）和高迁移率组框 1（HMGB1，炎症相关蛋白）的水平，并抑制了慢性收缩性损伤大鼠或脂多糖诱导的 BV-2 细胞中神经元的凋亡。然而，在脂多糖诱导的 BV-2 细胞中过表达 HSP90AA1 会抵消这些作用。BV-2细胞的外泌体可被小鼠星形胶质细胞吸收。此外，HSP90AA1的过表达逆转了芍药苷对与外泌体共培养的小鼠星形胶质细胞中HMGB1表达以及炎症因子和蛋白的影响。总之，芍药苷通过HSP90AA1/HMGB1途径调节小胶质细胞-星形胶质细胞的串联，从而缓解神经病理性疼痛并抑制慢性收缩性损伤的炎症反应，这进一步证明了芍药苷在治疗神经病理性疼痛方面的潜力。

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引用次数: 0

Alteration of N-glycosylation of CDON promotes H2O2-induced DNA damage in H9c2 cardiomyocytes CDON的N-糖基化改变会促进H9c2心肌细胞中由H2O2诱导的DNA损伤。

IF 3.4 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

International Journal of Biochemistry & Cell Biology

Pub Date : 2024-10-09 DOI: 10.1016/j.biocel.2024.106671

Liping Chen , Hongfei Liu , Wenxing Zhan , Changkun Long , Fang Xu , Xueer Li , Xiao-Li Tian , Shenghan Chen

Protein glycosylation is involved in DNA damage. Recently, DNA damage has been connected with the pathogenesis of heart failure. Cell adhesion associated, oncogene regulated (CDON), considered as an N-linked glycoprotein, is a transmembrane receptor for modulating cardiac function. But the role of CDON and its glycosylation in DNA damage remains unknown. In this study, we found that the knockdown of CDON caused DNA double-strand breaks as indicated by an increase in phosphorylated histone H2AX (γH2AX) protein level, immunofluorescent intensity of γH2AX and tail DNA moment in H9c2 cardiomyocytes. Conversely, overexpression of CDON led to decreasing DNA damage induced by hydrogen peroxide (H₂O₂) and upregulating the expression of genes related to DNA repair pathways-homologous recombination (HR) and non-homologous end joining (NHEJ). Moreover, we expressed nine predicted N-glycosylation site mutants in H9c2 cells prior to treatment with H₂O₂. The results showed that mutation of N-glycosylation sites (N99Q, N179Q, and N870Q) increased the accumulation of DNA damage and downregulated the expression of HR-related genes, demonstrating that CDON N-glycosylation on DNA damage is site-specific and these specific N-glycan sites may regulate HR repair-related transcript abundance of genes. Our data highlight that N-glycosylation of CDON is critical to cardiomyocyte DNA lesion. It may uncover the potential strategies targeting DNA damage pathway in heart disease.

蛋白质糖基化与 DNA 损伤有关。最近，DNA 损伤与心力衰竭的发病机制有关。细胞粘附相关癌基因调控（CDON）被认为是一种N-连接糖蛋白，是一种调节心脏功能的跨膜受体。但 CDON 及其糖基化在 DNA 损伤中的作用仍然未知。在本研究中，我们发现敲除 CDON 会导致 DNA 双链断裂，表现为磷酸化组蛋白 H2AX（γH2AX）蛋白水平、γH2AX 免疫荧光强度和 H9c2 心肌细胞尾部 DNA 矩的增加。相反，CDON的过表达会降低过氧化氢（H2O2）诱导的DNA损伤，并上调DNA修复途径--同源重组（HR）和非同源末端连接（NHEJ）相关基因的表达。此外，我们还在H9c2细胞中表达了9个预测的N-糖基化位点突变体，然后再用H2O2处理。结果表明，N-糖基化位点（N99Q、N179Q和N870Q）的突变增加了DNA损伤的积累，并下调了HR相关基因的表达，这表明CDON在DNA损伤上的N-糖基化是位点特异性的，这些特定的N-糖基化位点可能调控HR修复相关基因的转录本丰度。我们的数据强调了CDON的N-糖基化对心肌细胞DNA损伤至关重要。这可能揭示了针对心脏病DNA损伤途径的潜在策略。

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