title: Hydrogen sulfide decreases high glucose/palmitate-induced autophagy in endothelial cells by the Nrf2-ROS-AMPK signaling pathway.
abstract: BACKGROUND
  Excessive autophagy induced by extravagant oxidative stress is the main reason for diabetes-induced vascular endothelial cells dysfunction. Hydrogen sulfide (H2S) has anti-oxidative effects but its regulation on excessive autophagy of vascular endothelial cells is unclear.
  
  
  METHODS
  In this study, aorta of db/db mice (28 weeks old) and rat aortic endothelial cells (RAECs) treated with 40 mM glucose and 500 μM palmitate acted as type II diabetic animal and cellular models, respectively, and 100 μMNaHS was used as an exogenous H2S donor. The apoptosis level was measured by terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling (TUNEL) staining and Hoechst 33342/PI staining. The activities of SOD, CAT and respiratory complexes were also measured. The mRNA levels of SOD and CAT were detected by real-time PCR. AMPK-siRNA was used to detect the effect of AMPK on autophagy. Western blotting was used to detected the protein level.
  
  
  RESULTS
  H2S production was decreased (p < 0.05, p < 0.01) both in vitro and in vivo; NaHS treatment rescued this impairment (p < 0.05, p < 0.01). The expression of adhesive proteins was increased (p < 0.05, p < 0.01) both in vitro and in vivo; NaHS attenuated (p < 0.05, p < 0.01) these alterations. NaHS could protect endothelial cells against apoptosis induced by type II diabetes (p < 0.05, p < 0.01). Furthermore, the expressions and activities of SOD and CAT were impaired (p < 0.05, p < 0.01) in endothelial cells of diabetes II; NaHS treatment attenuated (p < 0.05) this impairment. NaHS also increased ATP production (p < 0.05) and activities of respiratory complexes (p < 0.05), and the ratio of p-AMPK to AMPK was also decreased by NaHS (p < 0.01). The level of autophagy in endothelial cells was also decreased (p < 0.05, p < 0.01) by NaHS treatment and AMPK-siRNA treatment. The expression of Nrf2 in the nuclei was increased (p < 0.05) by NaHS treatment.
  
  
  CONCLUSIONS
  Exogenous H2S might protect arterial endothelial cells by suppressing excessive autophagy induced by oxidative stress through the Nrf2-ROS-AMPK signaling pathway.
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Harbin, 150086 China.
authors.forename: Jiaqi
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Harbin, 150086 China.
authors.forename: Jichao
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Harbin, 150086 China.
authors.forename: Aili
authors.initials: A
authors.lastname: Sun
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Harbin, 150086 China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Harbin, 150086 China.
authors.forename: Xiangjing
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Harbin, 150086 China.
authors.forename: Ning
authors.initials: N
authors.lastname: Liu
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Harbin, 150086 China.
authors.forename: Shiyun
authors.initials: S
authors.lastname: Dong
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Harbin, 150086 China.
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Harbin, 150086 China.
authors.forename: Linxue
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Harbin, 150086 China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhong
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Harbin, 150086 China.
authors.forename: Changqing
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Harbin, 150086 China.
authors.forename: Fanghao
authors.initials: F
authors.lastname: Lu
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Harbin, 150086 China.
authors.forename: Weihua
authors.initials: W
authors.lastname: Zhang
keywords: Autophagy; Hydrogen sulfide; Oxidative stress; Type II diabetes; Vascular endothelial cells