<p>Hydrogen Sulfide Protects Against High Glucose-Induced Human Umbilical Vein Endothelial Cell Injury Through Activating PI3K/Akt/eNOS Pathway</p>

Abstract

Dysfunction of endothelial cells plays a key role in the pathogenesis of diabetic atherosclerosis. High glucose (HG) has been found as a key factor in the progression of diabetic complications, including atherosclerosis. PI3K/Akt/eNOS signaling pathway has been shown to involve in HG-induced vascular injuries. Hydrogen sulfide (H 2 S) has been found to exhibit protective effects on HG-induced vascular injuries. Moreover, H 2 S activates PI3K/Akt/eNOS pathway in endothelial cells. Thus, the present study aimed to determine if H 2 S exerts protective effects against HG-induced injuries of human umbilical vein endothelial cells (HUVECs) via activating PI3K/Akt/eNOS signaling. Materials and Methods: The endothelial protective effects of H 2 S were evaluated and compared to the controlled groups. Cell viability, cell migration and tube formation were determined by in vitro functional assays; protein levels were evaluated by Western blot assay and ELISA; cell apoptosis was determined by Hoechst 33258 nuclear staining; Reactive oxygen species (ROS) production was evaluated by the ROS detection kit. Results: HG treatment significantly inhibited PI3K/Akt/eNOS signaling in HUVECs, which was partially reversed by the H2S treatment. HG treatment inhibited cell viability of HUVECs, which were markedly prevented by H 2 S or PI3K agonist Y-P 740. HG treatment also induced HUVEC cell apoptosis by increasing the protein levels of cleaved caspase 3, Bax and Bcl-2, which were significantly attenuated by H 2 S or 740 Y-P. ROS production and gp91 phox protein level were increased by HG treatment in HUVECs and this effect can be blocked by the treatment with H 2 S or Y-P 740. Moreover, HG treatment increased the protein levels of pro-inflammatory cytokines, caspase-1 and phosphorylated JNK, which was significantly attenuated by H 2 S or Y-P 740. Importantly, the cytoprotective effect of H 2 S against HG-induced injury was inhibited by LY294002 (an inhibitor of PI3K/Akt/eNOS signaling pathway). Conclusion: The present study demonstrated that exogenous H 2 S protects endothelial cells against HG-induced injuries by activating PI3K/Akt/eNOS pathway. Based on the above findings, we proposed that reduced endogenous H 2 S levels and the subsequent PI3K/Akt/ eNOS signaling impairment may be the important pathophysiological mechanism underlying hyperglycemia-induced vascular injuries.

Interleukin-25-Mediated-IL-17RB Upregulation Promotes Cutaneous Wound Healing in Diabetic Mice by Improving Endothelial Cell Functions

“…It has been suggested that activation of AKT and ERK 1/2 pathways are able to optimize cellular functions and promote endothelial cell survival and tube formation (38,56). HG damages endothelial cell function by inhibiting AKT and ERK 1/2 pathways (57,58). DM down-regulates the activation of AKT and ERK 1/2, resulting in delayed wound healing by decreasing proliferation and increasing cellular apoptosis (59), whereas activation of AKT and ERK 1/2 accelerates not only corneal wound healing but also cutaneous wound closure (37)(38)(39).…”

Nitric oxide inhibits endothelial cell apoptosis by inhibiting cysteine‐dependent SOD1 monomerization

“…The physiological concentration of NO produced by eNOS has anti-apoptotic and cytoprotective effects [39,40]. Andrographolide, hydrogen sulfide, and oxymatrine were reported to inhibit endothelial cell apoptosis through upregulating Akt/eNOS pathway [41][42][43]. Moreover, eNOS deficiency increased endothelial cell apoptosis and aggravated renal injury in mice with remnant kidney [44].…”

Effects of Levistilide A on Hemorheology and Endothelial Cell Injury in Rats with Blood Stasis

“…The protective effect of TCM and its components on endothelial cells is well recognized [ 41 – 43 ]. Most studies demonstrated the involvement of the PI3K-AKT signaling pathway, among which the expression of eNOs is regulated affecting the NO levels [ 44 – 46 ]. This signaling molecule acts widely in the body involved vasodilation and circulation, regulation of inflammation, and platelet activity, while ET has a strong vasoconstrictor effect.…”