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齐志涛, 闫冬, 熊凡, 昌鸣先. 鱼类和哺乳类Bcl-2家族蛋白的研究进展[J]. 水生生物学报, 2021, 45(4): 935-944. DOI: 10.7541/2021.2020.192
引用本文: 齐志涛, 闫冬, 熊凡, 昌鸣先. 鱼类和哺乳类Bcl-2家族蛋白的研究进展[J]. 水生生物学报, 2021, 45(4): 935-944. DOI: 10.7541/2021.2020.192
QI Zhi-Tao, YAN Dong, XIONG Fan, CHANG Ming-Xian. PROGRESSES OF BCL-2 PROTEINS IN TELEOST FISH AND MAMMALS[J]. ACTA HYDROBIOLOGICA SINICA, 2021, 45(4): 935-944. DOI: 10.7541/2021.2020.192
Citation: QI Zhi-Tao, YAN Dong, XIONG Fan, CHANG Ming-Xian. PROGRESSES OF BCL-2 PROTEINS IN TELEOST FISH AND MAMMALS[J]. ACTA HYDROBIOLOGICA SINICA, 2021, 45(4): 935-944. DOI: 10.7541/2021.2020.192

鱼类和哺乳类Bcl-2家族蛋白的研究进展

PROGRESSES OF BCL-2 PROTEINS IN TELEOST FISH AND MAMMALS

  • 摘要: 细胞凋亡, 即细胞程序性死亡, 在多细胞生物的发育和稳态调控过程中发挥关键作用。Bcl-2家族蛋白是凋亡过程中的主要调控因子, 关于Bcl-2家族蛋白在凋亡过程中的功能及其作用机制一直是研究的热点。已有研究显示Bcl-2家族蛋白不仅作用于线粒体引发凋亡, 并且参与了包括对细胞内质网Ca2+的调控、DNA损伤的修复及与自噬的相互作用等多种反应, 从多方面对细胞的生存状态进行调控。Bcl-2家族蛋白保守存在于脊椎动物和无脊椎动物中, 其功能在进化中存在异同。文章以高等脊椎动物(哺乳动物)和低等脊椎动物(硬骨鱼类)为代表, 总结了近年来Bcl-2家族蛋白在调控宿主凋亡与自噬、DNA损伤及新陈代谢等方面取得的最新进展。该研究为深入了解鱼类和哺乳类Bcl-2家族蛋白的功能和作用机制提供了重要参考。

     

    Abstract: Apoptosis (programmed cell death) plays key roles in the development and homeostasis of multicellular organisms. B-cell lymphoma 2 (Bcl-2) family proteins are the major regulators in the process of apoptosis. According to the presence of conserved Bcl-2 homology (BH) domains and functions in apoptosis, the Bcl-2 family can be classified into three subfamilies. The anti-apoptotic subfamily suppresses apoptotic which contains four BH domains (BH1-4) and mainly includes Bcl-2, Bcl-xL, myeloid cell leukemia 1 (Mcl-1), A1, Bcl-B and Bcl-w. The pro-apoptotic subfamily also contains four BH domains and includes Bax, Bak and Bok. BH-3 only subfamily acts as pro-apoptotic proteins, but contains only BH3 domain which includes Bid, Bad, Bmf, Bik, Puma, Noxa, Hrk and Bnip3. Previous studies revealed that the Bcl-2 family proteins were multifunctional proteins, which not only act on mitochondria to induce apoptosis, but also participate in a variety of reactions including regulation of Ca2+ in the endoplasmic reticulum (ER), repair of DNA damage, interaction with autophagy proteins, and regulation of cell survival. In the present review, the functions of Bcl-2 proteins in mammals and fish were analyzed and compared, hoping to find the functional similarities and differences between mammalian and fish Bcl-2 proteins. For the regulation of cell apoptosis, mammalian Bcl-2 proteins (Bcl-2, Bcl-xL, Bax, Bak) mainly regulate the process of mitochondrial outer membrane permeabilization (MOMP). Fish Bcl-2 proteins, such as Mcl-1, Bad and Bcl-xL, can also involve in the MOMP process during virus infection to regulate cell apoptosis. Mammalian Bcl-2 proteins regulate the inositol 1, 4, 5-trisphosphate receptor (IP3R) mediated Ca2+ release in the ER. Fish Nrz can interact with IP3R1 to regulate Ca2+ release in ER. In addition, fish Bid and Bax can regulate Ca2+ release in ER through the ryanodine receptor (RyR) signaling pathway. Mammalian Bid, Bcl-xL and Puma involve in the reparations of DNA damage. Studies on the functions of Bcl-2 proteins in fish in DNA damage were limited. During DNA damage, fish Noxa was downregulated and Bcl-2 was upregulated, leading to the inhibition of apoptosis and keeping the embryos survive from the paternal DNA damage. In the process of autophagy, mammalian Bcl-2 proteins (Bcl-2, Bcl-xL, Bcl-w and Mcl-1) can inhibit autophagy by binding with autophagy gene Beclin-1. Fish p53 inhibit Bnip3 to protect the cell death caused by hypoxia. Mammalian Bad, Noxa and Bnips involve in the glycometabolism and lipid metabolism. Whilst, research on fish Bcl-2 in metabolism is scarce. Palmitic acid (PA) adding diet can increase the expression of Bim, Bid and Bax in zebrafish, indicating that fish Bcl-2 proteins also play roles in metabolism, but the mechanisms need further study. This review provides important reference for understanding the functions and mechanisms of Bcl-2 family proteins in fish and mammals.

     

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