Cellular signalling最新文献_第7页

SYT15B promotes tumor progression through interaction with IQGAP1 to activate the MAPK pathway in lung adenocarcinoma SYT15B在肺腺癌中通过与IQGAP1相互作用激活MAPK通路促进肿瘤进展。

IF 3.7 2区生物学 Q2 CELL BIOLOGY

Cellular signalling

Pub Date : 2025-12-07 DOI: 10.1016/j.cellsig.2025.112302

Yue Ren , Tianyi Li , Heng Zhou , Yuqing Cui , Chenghao Li , Weigan Shen , Haibo Sun , Haiyan Mao , Zhengrong Zhang , Zheng Wang , Zhi Ling , Yong Chen , Xudong Yin

Lung adenocarcinoma (LUAD) the predominant subtype of lung cancer, is characterized by rapid tumor growth, local invasion, and distant metastasis. Since dysregulated expression of synaptotagmin (SYT) proteins have been implicated in the development and progression of LUAD, the specific role and mechanisms of SYT15B in LUAD remain unclear. This study demonstrates that elevated SYT15B expression drives malignant progression and predicts poor prognosis in LUAD, as evidenced by integrated clinical sample, in vitro, and in vivo analyses. We identify a novel molecular mechanism whereby SYT15B interacts with IQ motif-containing GTPase-activating protein 1 (IQGAP1), leading to activation of the MAPK signalling pathway and subsequent promotion of aggressive tumor phenotypes. Disruption of the SYT15B-IQGAP1 interaction through IQGAP1 knockdown attenuated MAPK signalling pathway activation and reversed the oncogenic phenotype induced by SYT15B. Notably, specific inhibition of intracellular calcium with BAPTA can also attenuates SYT15B-IQGAP1 complex formation, abrogates MAPK signalling activation, and reverses SYT15B-mediated oncogenic effects. These findings establish the calcium-dependent SYT15B/IQGAP1/MAPK axis as a potential therapeutic and prognostic biomarker in LUAD.

肺腺癌（LUAD）是肺癌的主要亚型，其特点是肿瘤生长迅速、局部侵袭和远处转移。由于SYT蛋白表达失调与LUAD的发生和发展有关，SYT15B在LUAD中的具体作用和机制尚不清楚。本研究通过综合临床样本、体外和体内分析表明，SYT15B表达升高可推动LUAD的恶性进展，并预测预后不良。我们发现了一种新的分子机制，即SYT15B与含有IQ基序的gtpase激活蛋白1 （IQGAP1）相互作用，导致MAPK信号通路的激活，并随后促进侵袭性肿瘤表型。通过IQGAP1敲低干扰SYT15B-IQGAP1相互作用可减弱MAPK信号通路的激活，逆转SYT15B诱导的致癌表型。值得注意的是，用BAPTA特异性抑制细胞内钙也可以减弱SYT15B-IQGAP1复合物的形成，消除MAPK信号激活，逆转syt15b介导的致癌作用。这些发现确立了钙依赖性SYT15B/IQGAP1/MAPK轴作为LUAD潜在的治疗和预后生物标志物。

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引用次数: 0

Decoding COPD-related cognitive impairment: The protective potential of YTHDF1 解码copd相关认知障碍：YTHDF1的保护潜力。

IF 3.7 2区生物学 Q2 CELL BIOLOGY

Cellular signalling

Pub Date : 2025-12-07 DOI: 10.1016/j.cellsig.2025.112311

Keke Lu , Yuanyuan Qu , Ruohuan Shi , Chao Wu , Tao Xu

Cognitive impairment is a significant complication in individuals with chronic obstructive pulmonary disease (COPD), which presents a substantial challenge to future healthcare resource allocation. However, the underlying therapeutic targets and mechanisms remain inadequately understood. In a study involving mice with COPD, hippocampal damage and deficits in working memory, spatial learning, and memory capabilities were observed following prolonged exposure to cigarette smoke (CS). CS exposure was found to induce apoptosis in hippocampal cells in vivo. Western blot and RT-qPCR analyses demonstrated a marked reduction in the expression of the m6A RNA-binding protein YTHDF1 compared to the control group. In vitro experiments related to the brain damage mechanism of COPD demonstrated a significant decrease in the level of YTHDF1 under hypoxic conditions. Notably, the overexpression of YTHDF1 mitigated hypoxia-induced apoptosis in HT22 cells. Furthermore, the overexpression of YTHDF1 attenuated cognitive impairment by reducing hippocampal neuronal apoptosis induced by CS. The findings suggest that YTHDF1 could have a substantial impact on cognitive dysfunction induced by COPD. Hypoxic conditions within hippocampal tissue may significantly contribute to this process, offering novel insights into the molecular mechanisms underlying COPD-related cognitive impairment.

认知障碍是慢性阻塞性肺疾病（COPD）患者的重要并发症，对未来的医疗资源分配提出了重大挑战。然而，潜在的治疗靶点和机制仍然不充分了解。在一项涉及COPD小鼠的研究中，观察到长时间暴露于香烟烟雾（CS）后海马损伤和工作记忆、空间学习和记忆能力的缺陷。CS暴露在体内可诱导海马细胞凋亡。Western blot和RT-qPCR分析显示，与对照组相比，m6A rna结合蛋白YTHDF1的表达明显减少。体外COPD脑损伤机制相关实验显示，缺氧条件下YTHDF1水平显著降低。值得注意的是，YTHDF1的过表达减轻了缺氧诱导的HT22细胞凋亡。此外，YTHDF1的过表达通过减少CS诱导的海马神经元凋亡来减轻认知功能障碍。研究结果表明，YTHDF1可能对COPD引起的认知功能障碍有重大影响。海马组织内的缺氧条件可能对这一过程有重要影响，为copd相关认知障碍的分子机制提供了新的见解。

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引用次数: 0

Reprogramming mitochondrial homeostasis in renal ischemia–reperfusion injury 肾缺血再灌注损伤中线粒体稳态重编程。

IF 3.7 2区生物学 Q2 CELL BIOLOGY

Cellular signalling

Pub Date : 2025-12-06 DOI: 10.1016/j.cellsig.2025.112294

Kangyu Wang , Hao Wang , Yalong Zhang , Zijian Zhang , Li Wang , Jianwei Yang , Jiangwei Man , Li Yang

Acute kidney injury (AKI) caused by renal ischemia–reperfusion injury (RIRI) is primarily a mitochondrial disorder characterized by disrupted dynamics, impaired biogenesis, and defective quality control. Excessive DRP1-mediated fission, suppression of the AMPK–SIRT–PGC-1α axis, and failure of the PINK1–Parkin mitophagy system converge to drive tubular dysfunction and ferroptosis. Here, we integrate recent insights into a “mitochondrial reprogramming” framework encompassing three axes—dynamic remodeling, metabolic renewal, and proteostatic reinforcement. Therapeutic strategies targeting these axes, such as DRP1 inhibition, AMPK–SIRT–PGC-1α activation, and reinforcement of mitophagy and MAM integrity by agents like melatonin, puerarin, or Schisandrin B, have shown promise in restoring mitochondrial resilience. Furthermore, mitochondrial biomarkers and imaging tools (mtDNA, mitochondrial peptides, [¹⁸F]BCPP-EF PET) may enable phenotype-guided interventions. This review outlines the “RIRI–Mitochondria–AKI–CKD continuum,” emphasizing that mitochondrial maladaptation bridges acute injury and chronic fibrosis, highlighting mitochondria as precision therapeutic targets in AKI.

由肾缺血再灌注损伤（RIRI）引起的急性肾损伤（AKI）主要是一种线粒体疾病，其特征是动力学破坏、生物发生受损和质量控制缺陷。过度的drp1介导的裂变，AMPK-SIRT-PGC-1α轴的抑制，以及PINK1-Parkin有丝分裂系统的失败共同驱动小管功能障碍和铁凋亡。在这里，我们将最近的见解整合到“线粒体重编程”框架中，该框架包括三个轴-动态重塑，代谢更新和蛋白质静态强化。针对这些轴的治疗策略，如DRP1抑制，AMPK-SIRT-PGC-1α激活，以及通过褪黑素、葛根素或五味子素B等药物增强线粒体自噬和MAM完整性，已经显示出恢复线粒体弹性的希望。此外，线粒体生物标志物和成像工具（mtDNA，线粒体肽，[18F]BCPP-EF PET）可以实现表型引导干预。这篇综述概述了“riri -线粒体-AKI- ckd连续体”，强调线粒体适应不良是急性损伤和慢性纤维化的桥梁，强调线粒体是AKI的精确治疗靶点。

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引用次数: 0

Far-infrared irradiation suppresses pyroptosis in ischemic flaps through TRPV3-mediated activation of the A2AR/EPAC1/Rap1 signaling pathway 远红外照射通过trpv3介导的A2AR/EPAC1/Rap1信号通路的激活抑制缺血皮瓣的焦亡。

IF 3.7 2区生物学 Q2 CELL BIOLOGY

Cellular signalling

Pub Date : 2025-12-05 DOI: 10.1016/j.cellsig.2025.112299

Yuqi Wang , Jiaying Lou , Rongfang Dai , Liang Chen , Yi Wang , Yu Wang , Xiangwei Ling , Xiaoqiong Jiang , Fuman Cai

Random pattern skin flaps (RPSFs) are often associated with distal ischemic necrosis, primarily due to inadequate blood perfusion. Although far-infrared (FIR) irradiation has been reported to promote tissue repair, its precise role and underlying mechanisms in ischemic flap survival remain poorly understood. Here, we demonstrated that FIR irradiation enhances ischemic flap survival by activating the Adenosine A2a receptor/Exchange protein activated by cAMP 1/Ras - related protein 1 (A2AR/EPAC1/Rap1) pathway through transient receptor potential cation channel subfamily V member 3 (TRPV3)-mediated Ca²⁺ influx and subsequent adenosine production, and by suppressing pyroptosis. Transcriptome sequencing indicated that A2AR was reduced in ischemic flaps. Inhibition of A2AR impairs angiogenesis, promotes oxidative stress and pyroptosis, thereby exacerbating ischemia in the flaps. FIR irradiation attenuates pyroptosis through the A2AR/EPAC1/Rap1 pathway, thereby mitigating ischemia in the flaps caused by A2AR deficiency. Furthermore, KEGG pathway analysis revealed that the calcium signaling pathway and transient receptor potential channels play a critical role in ischemic flaps. Silencing TRPV3 in both mice and endothelial cells revealed that FIR upregulated TRPV3 expression, promoted extracellular Ca²⁺ influx, triggered ATP conversion to adenosine, and subsequently activated A2AR. Overall, this study provides new insights into the therapeutic mechanisms of FIR irradiation in ischemic flaps, offering potential targets for improving the treatment of ischemic flap pathology.

随机皮瓣（RPSFs）通常与远端缺血性坏死有关，主要是由于血液灌注不足。尽管有报道称远红外（FIR）照射可促进组织修复，但其在缺血皮瓣存活中的确切作用和潜在机制尚不清楚。在这里，我们证明了FIR照射通过瞬时受体电位阳离子通道亚家族V成员3 （TRPV3）介导的Ca2+内流和随后的腺苷生成，激活由cAMP 1/Ras相关蛋白1 （A2AR/EPAC1/Rap1）激活的腺苷A2a受体/交换蛋白，并通过抑制焦亡，从而提高缺血皮瓣的存活。转录组测序显示，A2AR在缺血皮瓣中减少。抑制A2AR损害血管生成，促进氧化应激和焦亡，从而加剧皮瓣缺血。FIR照射通过A2AR/EPAC1/Rap1通路减弱焦亡，从而减轻A2AR缺乏引起的皮瓣缺血。此外，KEGG通路分析显示钙信号通路和瞬时受体电位通道在缺血皮瓣中起关键作用。在小鼠和内皮细胞中沉默TRPV3表明，FIR上调TRPV3的表达，促进细胞外Ca2+内流，触发ATP转化为腺苷，随后激活A2AR。总的来说，本研究为FIR照射缺血性皮瓣的治疗机制提供了新的见解，为改善缺血性皮瓣病理治疗提供了潜在的靶点。

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引用次数: 0

M6A reader IGF2BP3 stabili1zes SLC7A11 to antagonize ferroptosis and promote gastric tumorigenesis M6A阅读器IGF2BP3稳定SLC7A11拮抗铁下垂，促进胃肿瘤发生。

IF 3.7 2区生物学 Q2 CELL BIOLOGY

Cellular signalling

Pub Date : 2025-12-04 DOI: 10.1016/j.cellsig.2025.112295

Yan Yang , Hong Ye , Shuming Qin , Min Lin , Yixiao Liu , Xiaomei Li

The RNA-binding protein IGF2BP3 is implicated in gastric cancer (GC) progression, yet its mechanisms remain incompletely understood. Here, we demonstrate that IGF2BP3 is highly expressed in GC tissues and correlates with poor prognosis. Clinical analyses revealed elevated IGF2BP3 levels in tumors compared to adjacent tissues, with overexpression linked to advanced pathological grading. Functional studies in GC cells showed that IGF2BP3 knockdown suppressed proliferation, migration, invasion, and G1/S cell cycle transition, while its overexpression promoted oncogenic phenotypes. In vivo xenograft experiments confirmed IGF2BP3's tumor-promoting role, with IGF2BP3 knockdown reducing tumor growth and Ki67 expression, whereas overexpression enhanced these parameters. Mechanistically, IGF2BP3 regulated ferroptosis by modulating mitochondrial morphology, intracellular iron accumulation, glutathione depletion, reactive oxygen species (ROS), and lipid peroxidation. Furthermore, IGF2BP3 stabilized SLC7A11 mRNA via N6-methyladenosine (m6A)-dependent mechanisms, as evidenced by reduced mRNA stability upon IGF2BP3 depletion and direct validation of m6A modifications on SLC7A11. Global m6A levels were also influenced by IGF2BP3 expression. Our findings establish IGF2BP3 as a multifaceted oncoprotein driving GC progression through cell cycle dysregulation, ferroptosis suppression, and m6A-mediated SLC7A11 stabilization, providing novel therapeutic targets for GC intervention.

rna结合蛋白IGF2BP3与胃癌（GC）进展有关，但其机制尚不完全清楚。本研究表明IGF2BP3在胃癌组织中高表达，并与不良预后相关。临床分析显示，与邻近组织相比，肿瘤中IGF2BP3水平升高，过度表达与晚期病理分级有关。在GC细胞中的功能研究表明，IGF2BP3敲低抑制增殖、迁移、侵袭和G1/S细胞周期转变，而其过表达促进致癌表型。体内异种移植实验证实了IGF2BP3的促瘤作用，IGF2BP3敲低可降低肿瘤生长和Ki67的表达，而过表达可增强这些参数。从机制上讲，IGF2BP3通过调节线粒体形态、细胞内铁积累、谷胱甘肽耗竭、活性氧（ROS）和脂质过氧化来调节铁下垂。此外，IGF2BP3通过n6 -甲基腺苷（m6A）依赖机制稳定SLC7A11 mRNA，这可以通过IGF2BP3耗用降低mRNA稳定性和m6A修饰SLC7A11的直接验证来证明。全球m6A水平也受IGF2BP3表达的影响。我们的研究结果表明，IGF2BP3是一个多方面的癌蛋白，通过细胞周期失调、铁凋亡抑制和m6a介导的SLC7A11稳定来驱动GC进展，为GC干预提供了新的治疗靶点。

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引用次数: 0

CAFs-EVs-miR-6765-3p promotes malignant progression of colorectal cancer by regulating aerobic glycolysis mediated by the GNG7/mTOR pathway cafs - ev - mir -6765-3p通过调节GNG7/mTOR途径介导的有氧糖酵解促进结直肠癌的恶性进展

IF 3.7 2区生物学 Q2 CELL BIOLOGY

Cellular signalling

Pub Date : 2025-12-04 DOI: 10.1016/j.cellsig.2025.112297

Cheng Xi, Zheng Zhang, Nianyuan Ye, Haifeng Tang, Wei Ding, Yibo Wang

Recently, the signaling interactions between cancer cells and stromal cells within the tumor microenvironment (TME) have been extensively studied. Cancer-associated fibroblasts (CAFs) serve as critical stromal components in the TME. Numerous studies have shown that CAFs promote cancer progression by delivering microRNAs (miRNAs) to colorectal cancer (CRC) cells. In this study, miR-6765-3p was found to be overexpressed in extracellular vesicles (EVs) secreted by CAFs (CAFs-EVs) and could be transferred to CRC cells, thereby enhancing malignant cell phenotypes. Further experiments have demonstrated that miR-6765-3p directly targets the 3′-untranslated region (UTR) of G protein γ 7 (GNG7). Mechanistically, we have collaboratively demonstrated through cellular and animal experiments that the overexpression of GNG7 reduces CRC progression mediated by miR-6765-3p in CAFs-EVs. Furthermore, GNG7 has been elucidated to suppress CRC development by inhibiting the phosphorylation of proteins involved in the mTOR pathway. It is important to emphasize that the mTOR pathway plays a key role in regulating aerobic glycolysis processes in cancer. Consistently, our study further demonstrated that CAFs-EVs activate aerobic glycolysis via the mTOR pathway by suppressing GNG7 expression. In summary, our findings suggest that CAFs-EVs carrying miR-6765-3p promote the malignant progression of CRC by modulating the GNG7/mTOR pathway to stimulate aerobic glycolysis.

近年来，肿瘤微环境（tumor microenvironment， TME）内癌细胞与基质细胞之间的信号相互作用得到了广泛的研究。癌症相关成纤维细胞（CAFs）在TME中是关键的基质成分。大量研究表明，CAFs通过向结直肠癌（CRC）细胞传递microRNAs （miRNAs）来促进癌症进展。本研究发现，miR-6765-3p在CAFs分泌的细胞外囊泡（ev）（CAFs- ev）中过表达，并可转移到CRC细胞中，从而增强恶性细胞表型。进一步的实验表明，miR-6765-3p直接靶向G蛋白γ 7 （GNG7）的3 ' -未翻译区（UTR）。在机制上，我们通过细胞和动物实验共同证明了GNG7的过表达减少了由miR-6765-3p在cafs - ev中介导的CRC进展。此外，GNG7已被阐明通过抑制mTOR通路中蛋白的磷酸化来抑制结直肠癌的发展。值得强调的是，mTOR通路在调节癌症的有氧糖酵解过程中起着关键作用。与此一致，我们的研究进一步证明，cafs - ev通过抑制GNG7的表达，通过mTOR途径激活有氧糖酵解。总之，我们的研究结果表明，携带miR-6765-3p的cafs - ev通过调节GNG7/mTOR通路刺激有氧糖酵解来促进CRC的恶性进展。

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引用次数: 0

Selenium-binding protein 1 suppresses cell cycle progression via cyclin-dependent kinase 2 breakdown in colon carcinoma 硒结合蛋白1通过细胞周期蛋白依赖性激酶2分解抑制结肠癌细胞周期进程。

IF 3.7 2区生物学 Q2 CELL BIOLOGY

Cellular signalling

Pub Date : 2025-12-04 DOI: 10.1016/j.cellsig.2025.112296

Xiaotian Zhang , Dong Zhang , Qichang Liu , Zhipeng Cao , Ju Yang , Liang Li , Runqi Hong , Zhiqing Hu , Jiankang Zhu , Rui Chen , Gengming Niu , Shanliang Han , Chongwei Ke , Liang Chen

Selenium-binding protein 1 (SELENBP1) may act as a tumor suppressor gene in colorectal cancer (CRC). However, it remains unclear whether SELENBP1 regulates cell cycle progression governed by cyclin-dependent kinase 2 (CDK2). Herein, we validated the intracellular binding of SELENBP1 to CDK2, based on our previous observations. We investigated the regulatory effects of SELENBP1 on retinoblastoma protein (RB) signaling pathway activation and CDK2-mediated cell cycle progression. Finally, we explored the molecular mechanism through which SELENBP1 inhibited CDK2 expression. Both ectopically induced and endogenously expressed SELENBP1 bound to CDK2 in cultured CRC cells. SELENBP1 inhibited the expression of CDK2 and activated RB signaling. Studies have indicated that SELENBP1 inhibits the cell cycle and suppresses tumor growth. Mechanistic studies showed that SELENBP1 might suppress cancer cell growth by causing CDK2 breakdown via ubiquitination. We conclude that SELENBP1 plays a distinct role as a potential tumor suppressor-associated gene that blocks the interphase and mitosis continuum and suppresses tumor growth in CRC by inducing the ubiquitination-mediated degradation of CDK2.

硒结合蛋白1 （SELENBP1）可能在结直肠癌（CRC）中发挥肿瘤抑制基因的作用。然而，SELENBP1是否调控由周期蛋白依赖性激酶2 （cyclin-dependent kinase 2, CDK2）调控的细胞周期进程尚不清楚。在此，基于我们之前的观察，我们验证了SELENBP1与CDK2的细胞内结合。我们研究了SELENBP1对视网膜母细胞瘤蛋白（RB）信号通路激活和cdk2介导的细胞周期进程的调节作用。最后，我们探讨了SELENBP1抑制CDK2表达的分子机制。在体外培养的结直肠癌细胞中，硒bp1结合CDK2在体外诱导和内源性表达。SELENBP1抑制CDK2的表达，激活RB信号。研究表明，SELENBP1抑制细胞周期，抑制肿瘤生长。机制研究表明，SELENBP1可能通过泛素化作用导致CDK2分解，从而抑制癌细胞生长。我们得出结论，SELENBP1作为一种潜在的肿瘤抑制相关基因发挥着独特的作用，它通过诱导泛素化介导的CDK2降解，阻断结直肠癌的间期和有丝分裂连续体，抑制肿瘤生长。

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引用次数: 0

Role of ferroptosis in gastric cancer 铁下垂在胃癌中的作用。

IF 3.7 2区生物学 Q2 CELL BIOLOGY

Cellular signalling

Pub Date : 2025-12-02 DOI: 10.1016/j.cellsig.2025.112293

Jia-Xing Xu , Ya-Mei Guo , Bo Wang , Yue-Yue Xie , Meng-Yuan Hao , Hong-Jie Li , Hang-Shen Han , Yan-Ge Li , Dong-Dong Wu

Gastric cancer remains a globally prevalent malignancy with significant clinical burdens. The iron-mediated cell death mechanism known as ferroptosis has gained substantial attention in cancer studies owing to its distinctive biological characteristics and disease-related implications. This review delineates the molecular machinery driving ferroptosis and systematically analyzes its dual roles in gastric carcinogenesis—both as a tumor-suppressive mechanism and a vulnerability axis during metastasis. Furthermore, we summarize the multi-layered regulatory networks governing ferroptosis, encompassing metabolic reprogramming, redox homeostasis, and microenvironmental crosstalk. By integrating preclinical and clinical evidence, this review proposes ferroptosis-targeted therapeutic strategies that synergize with conventional therapies, highlighting their potential to overcome drug resistance and reshape immunosuppressive niches. These insights bridge mechanistic understanding with translational research, offering a framework for advancing precision interventions in gastric cancer management.

胃癌（GC）仍然是一种普遍的全球恶性肿瘤，具有显著的临床负担。铁介导的细胞死亡机制被称为铁下垂，由于其独特的生物学特性和疾病相关意义，在癌症研究中获得了大量关注。本文综述了铁下垂的分子机制，并系统分析了其在胃癌发生中的双重作用——既是肿瘤抑制机制，又是转移过程中的易损性轴。此外，我们研究了控制铁死亡的多层调控网络，包括代谢重编程、氧化还原稳态和微环境串扰。通过整合临床前和临床证据，本研究提出了与传统疗法协同作用的铁中毒靶向治疗策略，强调了它们克服耐药性和重塑免疫抑制利基的潜力。这些见解将机制理解与转化研究联系起来，为推进GC管理中的精确干预提供了一个框架。

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引用次数: 0

ATP alleviates heat stress-induced suppression of proliferation and enhancement of apoptosis by inhibiting the activation of AMPK/mTORC1 signaling in the Sertoli cells of dairy bulls ATP通过抑制奶牛支持细胞AMPK/mTORC1信号的激活，缓解热应激诱导的增殖抑制和凋亡增强。

IF 3.7 2区生物学 Q2 CELL BIOLOGY

Cellular signalling

Pub Date : 2025-12-02 DOI: 10.1016/j.cellsig.2025.112291

Haodi Zhang , Haotian Lan , Yue Guo , Xiaoyu Sun , Wei Zhang , Benge Zou , Shiyong Zhu , Zhongling Jiang , Huatao Li , Rongfeng Cao , Kaiqiang Fu

Sertoli cells (SCs), as essential somatic cells in the testes of dairy bulls, offer both structural and nutrient assistance to developing germ cells while interacting directly with them to regulate spermatogenesis. AMP-activated protein kinase (AMPK) functions as an essential regulator of energy metabolism in the testis. However, the regulatory function of AMPK in maintaining SC viability during heat stress conditions is unclear. Recent research has focused on the protective function of ATP in the modulation of SC enhancement of apoptosis and suppression of proliferation under heat stress conditions through AMPK/mTORC1 signaling. The present study demonstrated that heat stress significantly suppressed cell proliferation and increased apoptosis in SCs. ATP pretreatment also prevented heat stress-related decreases in the mitochondrial membrane potential and mRNA expression levels of PCNA and KI67 (both are markers of cell proliferation and indicate the proliferation status of cells through different mechanisms). Moreover, ATP treatment reversed the effects of heat stress on cell proliferation and apoptosis, and ATP treatment increased cell viability by alleviating the expression of the AMPK/mTORC1 signaling-related components in heat stress-induced SCs. In summary, these findings indicate that AMPK/mTORC1 signaling is involved in the regulation of apoptosis and proliferation in SCs during heat stress and that the protective effects of ATP therapy on SCs provide a theoretical basis for preventing heat stress injury in the testes of dairy bulls.

支持细胞（SCs）是奶牛睾丸中必不可少的体细胞，为生殖细胞的发育提供结构和营养援助，并直接与生殖细胞相互作用，调节精子的发生。amp活化蛋白激酶（AMPK）是睾丸能量代谢的重要调节因子。然而，AMPK在热应激条件下维持SC活力的调节功能尚不清楚。最近的研究集中在ATP在热应激条件下通过AMPK/mTORC1信号通路调节SC、增强细胞凋亡和抑制细胞增殖中的保护作用。本研究表明，热应激显著抑制细胞增殖，增加细胞凋亡。ATP预处理还可以阻止热应激相关的线粒体膜电位和PCNA和KI67 mRNA表达水平的下降（两者都是细胞增殖的标志，通过不同的机制表明细胞的增殖状态）。此外，ATP处理逆转了热应激对细胞增殖和凋亡的影响，ATP处理通过减轻热应激诱导的sc中AMPK/mTORC1信号相关成分的表达来提高细胞活力。综上所述，上述研究结果表明AMPK/mTORC1信号通路参与热应激过程中SCs凋亡和增殖的调控，ATP对SCs的保护作用为预防奶牛睾丸热应激损伤提供了理论依据。

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引用次数: 0

Oxeiptosis in Parkinson's disease: Unraveling the KEAP1/PGAM5/AIFM1 Axis and its role in pathophysiology and therapeutics 帕金森病的氧上亢：解开KEAP1/PGAM5/AIFM1轴及其在病理生理和治疗中的作用

IF 3.7 2区生物学 Q2 CELL BIOLOGY

Cellular signalling

Pub Date : 2025-12-01 DOI: 10.1016/j.cellsig.2025.112288

Zongting Rong , Tingting Liu , Jianshe Wei

Parkinson's Disease (PD) is characterized by the progressive loss of dopaminergic neurons, a process where programmed cell death (PCD) plays a central role. Oxeiptosis, a caspase-independent, reactive oxygen species (ROS)-induced PCD pathway discovered in 2018 and mediated by the Kelch-like ECH-associated protein 1 (KEAP1)/phosphoglycerate mutase 5 (PGAM5)/apoptosis-inducing factor mitochondria-associated 1 (AIFM1) axis, has emerged as a key mechanism in PD pathophysiology. This review aims to systematically elaborate on the activation mechanism of the KEAP1/PGAM5/AIFM1 signaling axis in PD. It critically analyzes how this pathway interacts with core pathological processes of PD, including mitochondrial dysfunction, neuroinflammation, and autophagic disorder, forming vicious cycles that drive disease progression. Furthermore, the review explores the significant potential and current challenges of targeting the oxeiptosis pathway as a novel neuroprotective therapeutic strategy for PD.

帕金森病（PD）的特征是多巴胺能神经元的进行性丧失，这一过程中程序性细胞死亡（PCD）起着核心作用。氧化凋亡是一种不依赖caspase的活性氧（ROS）诱导的PCD途径，于2018年被发现，由kelch样ech相关蛋白1 (KEAP1)/磷酸甘油酸突变酶5 (PGAM5)/凋亡诱导因子线粒体相关1 （AIFM1）轴介导，已成为PD病理生理的关键机制。本文旨在系统阐述PD中KEAP1/PGAM5/AIFM1信号轴的激活机制。它批判性地分析了该途径如何与PD的核心病理过程相互作用，包括线粒体功能障碍、神经炎症和自噬障碍，形成驱动疾病进展的恶性循环。此外，本文还探讨了靶向氧化下垂通路作为PD的一种新的神经保护治疗策略的重大潜力和当前的挑战。

引用次数: 0