自噬通过溶酶体分解和循环利用细胞成分,促进细胞质量控制和能量代谢。作为自噬的一种形式,分子伴侣介导的自噬(chaperone-mediated autophagy, CMA)选择性降解细胞内含有KFERQ五肽的受损或异常蛋白,在维持细胞稳态中具有核心作用。近...自噬通过溶酶体分解和循环利用细胞成分,促进细胞质量控制和能量代谢。作为自噬的一种形式,分子伴侣介导的自噬(chaperone-mediated autophagy, CMA)选择性降解细胞内含有KFERQ五肽的受损或异常蛋白,在维持细胞稳态中具有核心作用。近期研究表明,CMA通过调控脂质代谢、细胞周期和氧化应激等途径,在消化系统疾病中发挥重要功能。作为CMA标志物的溶酶体相关膜蛋白2A (lysosomal-associated membrane protein 2A, LAMP2A)有望成为诊断、预后及治疗消化系统疾病的潜在靶点。本文总结了CMA在肝癌、胃肠肿瘤、脂肪性肝病及炎性肠病等方面的研究进展,为相关疾病的临床诊疗提供新的视角。Autophagy promotes cellular quality control and energy metabolism by degrading and recycling essential cellular components via lysosomes. As a form of autophagy, Chaperone mediated autophagy (CMA) selectively degrades damaged or dysfunctional proteins containing the KFERQ motif within the cell, playing a central role in maintaining cellular homeostasis. Recent studies indicate that CMA regulates critical processes such as cell cycle, oxidative stress, and lipid metabolism, significantly influencing digestive system diseases. Lysosomal-associated membrane protein 2A (LAMP2A), a CMA marker, holds promise as a potential target for diagnosis, prognosis, and therapy. This review highlights CMA research progress in liver cancer, gastrointestinal tumors, fatty liver disease, and inflammatory bowel diseases, offering new perspectives for clinical management.展开更多
文摘自噬通过溶酶体分解和循环利用细胞成分,促进细胞质量控制和能量代谢。作为自噬的一种形式,分子伴侣介导的自噬(chaperone-mediated autophagy, CMA)选择性降解细胞内含有KFERQ五肽的受损或异常蛋白,在维持细胞稳态中具有核心作用。近期研究表明,CMA通过调控脂质代谢、细胞周期和氧化应激等途径,在消化系统疾病中发挥重要功能。作为CMA标志物的溶酶体相关膜蛋白2A (lysosomal-associated membrane protein 2A, LAMP2A)有望成为诊断、预后及治疗消化系统疾病的潜在靶点。本文总结了CMA在肝癌、胃肠肿瘤、脂肪性肝病及炎性肠病等方面的研究进展,为相关疾病的临床诊疗提供新的视角。Autophagy promotes cellular quality control and energy metabolism by degrading and recycling essential cellular components via lysosomes. As a form of autophagy, Chaperone mediated autophagy (CMA) selectively degrades damaged or dysfunctional proteins containing the KFERQ motif within the cell, playing a central role in maintaining cellular homeostasis. Recent studies indicate that CMA regulates critical processes such as cell cycle, oxidative stress, and lipid metabolism, significantly influencing digestive system diseases. Lysosomal-associated membrane protein 2A (LAMP2A), a CMA marker, holds promise as a potential target for diagnosis, prognosis, and therapy. This review highlights CMA research progress in liver cancer, gastrointestinal tumors, fatty liver disease, and inflammatory bowel diseases, offering new perspectives for clinical management.
文摘目的:探讨癫痫大鼠海马氧化应激反应和分子伴侣介导的自噬(chaperone-mediated autophagy,CMA)活性的变化,以及抗氧化剂抗坏血酸(ascorbic acid,AA)神经保护作用的可能机制。方法:实验大鼠分为空白对照组、癫痫24 h组、AA预处理癫痫组和AA对照组。应用RT-PCR和免疫印迹法检测海马组织2a型溶酶体相关膜蛋白(lysosome-associated membrane protein type 2a,LAMP2a)mRNA和蛋白的变化,采用化学法检测海马组织丙二醛(malondialdehyde,MDA)和超氧化物歧化酶(superoxide dismutase,SOD)的水平。结果:癫痫组大鼠海马组织LAMP2a转录和合成明显高于空白对照组,MDA含量明显升高,而SOD的水平显著下降。AA预处理可显著减低癫痫大鼠海马LAMP2a的转录和合成,并明显降低MDA的含量,却显著提高SOD的水平。结论:癫痫发作导致的海马损伤时存在CMA激活现象和显著的氧化应激反应;抗氧化剂AA通过抑制CMA活性和降低氧化应激反应来减轻癫痫发作中的海马损伤,具有神经保护作用。
