Hydrogen sulfide facilities production of nitric oxide via the Akt/endothelial nitric oxide synthases signaling pathway to protect human umbilical vein endothelial cells from injury by angiotensin II

Abstract

Angiotensin II (Ang II) has been reported as key in inducing endothelial cell injury, and endothelial cells may produce nitric oxide (NO) to protect themselves. However, the underlying mechanism remains elusive. Human umbilical vein endothelial cells (HUVECs) were divided into five treatment groups as follows: Normal control, Ang II, Ang II + sodium hydrosulfide [NaHS; hydrogen sulfide (H2S) donor], Ang II + Akt inhibitors + NaHS, and Ang II + endothelial nitric oxide synthases (eNOS) inhibitors + NaHS. Subsequently, cell viability, apoptosis, migration, proliferation and adhesion ability were determined. In addition, tubular structure formation was observed, and the NO and phosphorylation levels of Akt and eNOS were evaluated. Compared with the normal control group, Ang II treatment reduced the viability of HUVECs and increased the level of cell apoptosis (P<0.05). Furthermore, Ang II treatment inhibited the phosphorylation level of eNOS and Akt, as well as the generation of NO (P<0.05). H2S reversed the above‑mentioned effects significantly and increased cell proliferation, adhesion ability and promoted tubular structure formation (P<0.05); however, H2S did not reverse the impact of eNOS and Akt phosphorylation levels after being processed with Akt and eNOS inhibitors, which indicates that H2S is capable of protecting HUVECs via the eNOS/Akt signaling pathway (P<0.05). Thus, H2S stimulates the production of NO and protects HUVECs via inducing the Akt/eNOS signaling pathway.

Sex Influence on Autophagy Markers and miRNAs in Basal and Angiotensin II-Treated Human Umbilical Vein Endothelial Cells

“…Among the parameters that become different with sex, there is cell viability: in FHUVECs, there is a small but not significant decrease in cell viability, whereas in male cells, it is significantly increased. This is in line with previous HUVEC cell lines of unknown sex [51,52], but in the majority of cases, it was shown that Ang II induced viability loss in HUVEC cell lines of unknown sex (an exhaustive list of references about this point is reported in Table S3 [ [53][54][55][56][57][58][59][60][61][62][63][64][65][66]). The discrepancy could be attributed to the use of HUVEC cell lines versus the primary cultures we used, and to different methods of culture and viability determination.…”

ACE Inhibitory Peptide from Skin Collagen Hydrolysate of Takifugu bimaculatus as Potential for Protecting HUVECs Injury

“…As presented in Figure 5e, L-NAME reduced Cap, and FNLRMQ improved NO production. Another study also showed a similar finding [60,61]. These results revealed that FNLRMQ had its effect on Ang-IIinduced cell dysfunction by activating the Akt/eNOS pathway, leading to NO production.…”

Gastrodin prevents homocysteine‐induced human umbilical vein endothelial cells injury via PI3K/Akt/eNOS and Nrf2/ARE pathway

“…Activated Akt regulates cell function by phosphorylating downstream factors such as enzymes, kinases and transcription factors 44 . The PI3K/Akt/eNOS signalling pathway regulates NO production through the phosphorylation of eNOS at Ser‐1177 under various stimuli 45 . In addition, phosphorylation of Akt promoted Nrf2 nuclear translation and activated downstream enzymes 46 .…”

“…44 The PI3K/Akt/eNOS signalling pathway regulates NO production through the phosphorylation of eNOS at Ser-1177 under various stimuli. 45 In addition, phosphorylation of Akt promoted Nrf2 nuclear translation and activated downstream enzymes. 46 Therefore, we blocked the phosphorylation of Akt by MK-2206 and found that the protective effects of Gas were abolished by the reduction of ROS, promotion of NO and nuclear translation of Nrf2.…”