Novel H2S donor proglumide-ADT-OH protects HUVECs from ox-LDL-induced injury through NF-κB and JAK/SATA pathway

Abstract

As a gaseous mediator, hydrogen sulfide (H2S) has many physiological effects and pathological effects in atherosclerosis. In recent years, many exogenous H2S donors have been synthesized to study atherosclerosis diseases. In this study, proglumide-(5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione) (P-A) was synthesized as a H2S donor. The protective effect and mechanism of P-A on HUVEC that was injured by ox-LDL were detected. The HUEVCs were affected by 100 μmol/L P-A for 24 h; the release of H2S was the largest. After 100 μmol/L P-A acted on HUVEC damage model for 12 h, the cell proliferation activity was the best. The results showed that P-A can downregulate the expression of p-NF-кBp65 protein and reduce the amount of TNF-α and IL-6 and promote the formation of IL-10 by inhibiting the NF-кB pathway, and also induce the expression of superoxide dismutase (SOD) to protect HUVEC from ox-LDL injury. P-A can also regulate JAK/STAT pathway to reduce the expression of p-JAK2 protein and reduce the production of IL-6 and TNF-α. P-A has protective effect on HUVEC injured by ox-LDL, and the protective mechanism is related to the regulation of JAK/STAT pathway and NF-кB pathway.

Keywords

• hydrogen sulfide donor
• atherosclerosis
• nf-кb
• jak/stat
• proglumide-(5-(4-hydroxyphenyl)-3h-1,2-dithiole-3-thione)