NBR1-mediated autophagic degradation of caspase 8 protects vascular endothelial cells against arsenite-induced apoptotic cell death

作者全名：Hu, Siyao; Wang, Fu; Mao, Lejiao; Jiang, Xuejun; Luo, Yilin; Qin, Xia; Zou, Zhen; Chen, Chengzhi; Yu, Chao; Zhang, Jun

作者地址：[Hu, Siyao; Yu, Chao] Chongqing Med Univ, Coll Pharm, Chongqing Key Lab Pharmaceut Metab Res, Chongqing 400016, Peoples R China; [Wang, Fu; Jiang, Xuejun; Chen, Chengzhi] Chongqing Med Univ, Sch Publ Hlth, Dept Occupat & Environm Hlth, Chongqing 400016, Peoples R China; [Mao, Lejiao; Luo, Yilin; Zou, Zhen; Zhang, Jun] Chongqing Med Univ, Inst Life Sci, Mol Biol Lab Resp Dis, Chongqing 400016, Peoples R China; [Qin, Xia] Chongqing Med Univ, Affiliated Hosp 1, Dept Pharm, Chongqing 400016, Peoples R China; [Zou, Zhen; Chen, Chengzhi; Zhang, Jun] Chongqing Med Univ, Res Ctr Environm & Human Hlth, Sch Publ Hlth, Chongqing 400016, Peoples R China

通信作者：Yu, C (通讯作者)，Chongqing Med Univ, Coll Pharm, Chongqing Key Lab Pharmaceut Metab Res, Chongqing 400016, Peoples R China.; Chen, CZ (通讯作者)，Chongqing Med Univ, Sch Publ Hlth, Dept Occupat & Environm Hlth, Chongqing 400016, Peoples R China.; Zhang, J (通讯作者)，Chongqing Med Univ, Inst Life Sci, Mol Biol Lab Resp Dis, Chongqing 400016, Peoples R China.; Chen, CZ; Zhang, J (通讯作者)，Chongqing Med Univ, Res Ctr Environm & Human Hlth, Sch Publ Hlth, Chongqing 400016, Peoples R China.

来源：BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:001236441000001

JCR分区：Q3

影响因子：2.5

年份：2024

卷号：715

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Apoptosis; Autophagy; Autophagy receptor; NBR1; Caspase 8 degradation

摘要：Vascular endothelial cells play a critical role in maintaining the health of blood vessels, but dysfunction can lead to cardiovascular diseases. The impact of arsenite exposure on cardiovascular health is a significant concern due to its potential adverse effects. This study aims to explore how NBR1-mediated autophagy in vascular endothelial cells can protect against oxidative stress and apoptosis induced by arsenite. Initially, our observations revealed that arsenite exposure increased oxidative stress and triggered apoptotic cell death in human umbilical vein endothelial cells (HUVECs). However, treatment with the apoptosis inhibitor Z-VAD-FMK notably reduced arsenite-induced apoptosis. Additionally, arsenite activated the autophagy pathway and enhanced autophagic flux in HUVECs. Interestingly, inhibition of autophagy exacerbated arsenite-induced apoptotic cell death. Our findings also demonstrated the importance of autophagy receptor NBR1 in arsenite-induced cytotoxicity, as it facilitated the recruitment of caspase 8 to autophagosomes for degradation. The protective effect of NBR1 against arsenite-induced apoptosis was compromised when autophagy was inhibited using pharmacological inhibitors or through genetic knockdown of essential autophagy genes. Conversely, overexpression of NBR1 facilitated caspase 8 degradation and reduced apoptotic cell death in arsenite-treated HUVECs. In conclusion, our study highlights the vital role of NBR1-mediated autophagic degradation of caspase 8 in safeguarding vascular endothelial cells from arsenite-induced oxidative stress and apoptotic cell death. Targeting this pathway could offer a promising therapeutic approach to mitigate cardiovascular diseases associated with arsenite exposure.

基金机构：National Natural Science Foundation of China [81500343]; Natural Science Foundation of Chongqing [cstc2022ycjh-bgzxm0101, CSTB2023NSCQ-MSX0312, KJQN202100405]; Science and Technology Research Program of Chongqing Municipal Education Commission [CQYC2020058650]; Chongqing Talents: Exceptional Young Talents Project [CYS22367]; Chongqing Graduate Student Research and Innovation Program [W0038]; Future Medical Youth Innovation Program of Chongqing Medical University [W0043, cstc2021ycjh-bgzxm0105]; Chongqing Bayu Talented Young Scholar program; [cstc2021jcyj-msxmX0141]

基金资助正文：This study was supported in part by the National Natural Science Foundation of China (81500343) , the Natural Science Foundation of Chongqing (cstc2021ycjh-bgzxm0105 cstc2022ycjh-bgzxm0101, cstc2021jcyj-msxmX0141, CSTB2023NSCQ-MSX0312) , the Science and Technology Research Program of Chongqing Municipal Education Commission (KJQN202100405) , the Chongqing Talents: Exceptional Young Talents Project (CQYC2020058650) , Chongqing Graduate Student Research and Innovation Program (CYS22367) and the Future Medical Youth Innovation Program of Chongqing Medical University (W0038 and W0043) . Additionally, J.Z., Z.Z., and C.C. receive support from the Chongqing Bayu Talented Young Scholar program.