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Exogenous hydrogen sulfide protects human umbilical vein endothelial cells against high glucose‑induced injury by inhibiting the necroptosis pathway.
Int J Mol Med 2018; 41(3):1477-1486IJ

Abstract

Hyperglycemia is a key factor in the development of diabetic complications, including the processes of atherosclerosis. Receptor‑interacting protein 3 (RIP3), a mediator of necroptosis, is implicated in atherosclerosis development. Additionally, hydrogen sulfide (H2S) protects the vascular endothelium against hyperglycemia‑induced injury and attenuates atherosclerosis. On the basis of these findings, the present study aimed to confirm the hypothesis that necroptosis mediates high glucose (HG)‑induced injury in human umbilical vein endothelial cells (HUVECs), and that the inhibition of necroptosis contributes to the protective effect of exogenous H2S against this injury. The results revealed that exposure of HUVECs to 40 mM HG markedly enhanced the expression level of RIP3, along with multiple injuries, including a decrease in cell viability, an increase in the number of apoptotic cells, an increase in the expression level of cleaved caspase‑3, generation of reactive oxygen species (ROS), as well as dissipation of the mitochondrial membrane potential (MMP). Treatment of the cells with sodium hydrogen sulfide (NaHS; a donor of H2S) prior to exposure to HG significantly attenuated the increased RIP3 expression and the aforementioned injuries by HG. Notably, treatment of cells with necrostatin‑1 (Nec‑1), an inhibitor of necroptosis, prior to exposure to HG ameliorated the HG‑induced injuries, leading to a decrease in ROS generation and a loss of MMP. However, pre‑treatment of the cells with Nec‑1 enhanced the HG‑induced increase in the expression levels of cleaved caspases‑3 and ‑9. By contrast, pre‑treatment with Z‑VAD‑FMK, a pan ‑caspase inhibitor, promoted the increased expression of RIP3 by HG. Taken together, the findings of the present study have demonstrated, to the best of our knowledge for the first time, that exogenous H2S protects HUVECs against HG‑induced injury through inhibiting necroptosis. The present study has also provided novel evidence that there is a negative interaction between necroptosis and apoptosis in the HG‑treated HUVECs.

Authors+Show Affiliations

Department of Endocrinology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangdong Geriatrics Institute, Guangzhou, Guangdong 510080, P.R. China.Department of Pediatrics, Huangpu Division of the First Affiliated Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510700, P.R. China.Department of Ultrasound, The First Affiliated Hospital, Sun Yat‑sen University, Guangzhou 510080, P.R. China.Department of Physiology, Zhongshan School of Medicine, Sun Yat‑sen University, Guangzhou 510080, P.R. China.Department of Endocrinology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangdong Geriatrics Institute, Guangzhou, Guangdong 510080, P.R. China.Department of Endocrinology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangdong Geriatrics Institute, Guangzhou, Guangdong 510080, P.R. China.Department of Endocrinology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangdong Geriatrics Institute, Guangzhou, Guangdong 510080, P.R. China.Department of Endocrinology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangdong Geriatrics Institute, Guangzhou, Guangdong 510080, P.R. China.Department of Physiology, Zhongshan School of Medicine, Sun Yat‑sen University, Guangzhou 510080, P.R. China.Department of Endocrinology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangdong Geriatrics Institute, Guangzhou, Guangdong 510080, P.R. China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29286079

Citation

Lin, Jiaqiong, et al. "Exogenous Hydrogen Sulfide Protects Human Umbilical Vein Endothelial Cells Against High Glucose‑induced Injury By Inhibiting the Necroptosis Pathway." International Journal of Molecular Medicine, vol. 41, no. 3, 2018, pp. 1477-1486.
Lin J, Chen M, Liu D, et al. Exogenous hydrogen sulfide protects human umbilical vein endothelial cells against high glucose‑induced injury by inhibiting the necroptosis pathway. Int J Mol Med. 2018;41(3):1477-1486.
Lin, J., Chen, M., Liu, D., Guo, R., Lin, K., Deng, H., ... Wu, W. (2018). Exogenous hydrogen sulfide protects human umbilical vein endothelial cells against high glucose‑induced injury by inhibiting the necroptosis pathway. International Journal of Molecular Medicine, 41(3), pp. 1477-1486. doi:10.3892/ijmm.2017.3330.
Lin J, et al. Exogenous Hydrogen Sulfide Protects Human Umbilical Vein Endothelial Cells Against High Glucose‑induced Injury By Inhibiting the Necroptosis Pathway. Int J Mol Med. 2018;41(3):1477-1486. PubMed PMID: 29286079.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Exogenous hydrogen sulfide protects human umbilical vein endothelial cells against high glucose‑induced injury by inhibiting the necroptosis pathway. AU - Lin,Jiaqiong, AU - Chen,Meiji, AU - Liu,Donghong, AU - Guo,Ruixian, AU - Lin,Kai, AU - Deng,Haiou, AU - Zhi,Ximei, AU - Zhang,Weijie, AU - Feng,Jianqiang, AU - Wu,Wen, Y1 - 2017/12/19/ PY - 2016/06/15/received PY - 2017/12/05/accepted PY - 2017/12/30/pubmed PY - 2018/8/4/medline PY - 2017/12/30/entrez SP - 1477 EP - 1486 JF - International journal of molecular medicine JO - Int. J. Mol. Med. VL - 41 IS - 3 N2 - Hyperglycemia is a key factor in the development of diabetic complications, including the processes of atherosclerosis. Receptor‑interacting protein 3 (RIP3), a mediator of necroptosis, is implicated in atherosclerosis development. Additionally, hydrogen sulfide (H2S) protects the vascular endothelium against hyperglycemia‑induced injury and attenuates atherosclerosis. On the basis of these findings, the present study aimed to confirm the hypothesis that necroptosis mediates high glucose (HG)‑induced injury in human umbilical vein endothelial cells (HUVECs), and that the inhibition of necroptosis contributes to the protective effect of exogenous H2S against this injury. The results revealed that exposure of HUVECs to 40 mM HG markedly enhanced the expression level of RIP3, along with multiple injuries, including a decrease in cell viability, an increase in the number of apoptotic cells, an increase in the expression level of cleaved caspase‑3, generation of reactive oxygen species (ROS), as well as dissipation of the mitochondrial membrane potential (MMP). Treatment of the cells with sodium hydrogen sulfide (NaHS; a donor of H2S) prior to exposure to HG significantly attenuated the increased RIP3 expression and the aforementioned injuries by HG. Notably, treatment of cells with necrostatin‑1 (Nec‑1), an inhibitor of necroptosis, prior to exposure to HG ameliorated the HG‑induced injuries, leading to a decrease in ROS generation and a loss of MMP. However, pre‑treatment of the cells with Nec‑1 enhanced the HG‑induced increase in the expression levels of cleaved caspases‑3 and ‑9. By contrast, pre‑treatment with Z‑VAD‑FMK, a pan ‑caspase inhibitor, promoted the increased expression of RIP3 by HG. Taken together, the findings of the present study have demonstrated, to the best of our knowledge for the first time, that exogenous H2S protects HUVECs against HG‑induced injury through inhibiting necroptosis. The present study has also provided novel evidence that there is a negative interaction between necroptosis and apoptosis in the HG‑treated HUVECs. SN - 1791-244X UR - https://www.unboundmedicine.com/medline/citation/29286079/Exogenous_hydrogen_sulfide_protects_human_umbilical_vein_endothelial_cells_against_high_glucose‑induced_injury_by_inhibiting_the_necroptosis_pathway_ L2 - http://www.spandidos-publications.com/ijmm/41/3/1477 DB - PRIME DP - Unbound Medicine ER -