L-cysteine and hydrogen sulfide increase PIP3 and AMPK/PPARγ expression and decrease ROS and vascular inflammation...

Area of Science:

• Biochemistry
• Molecular Biology
• Endocrinology

Background:

• Diabetic patients exhibit reduced L-cysteine (LC) and hydrogen sulfide (H2S) levels, correlating with increased vascular inflammation.
• Impaired LC and H2S metabolism are implicated in the pathogenesis of diabetic vascular complications.

Purpose of the Study:

• To investigate the role of L-cysteine (LC) and hydrogen sulfide (H2S) in modulating vascular inflammation markers in a high-glucose diabetes model.
• To elucidate the molecular mechanisms underlying the protective effects of LC and H2S against high-glucose-induced cellular damage.

Main Methods:

• Human U937 monocytic cells were exposed to high glucose (HG) and treated with L-cysteine (LC) or sodium sulfide (Na2S).
• Key signaling pathways, including PI3K/PIP3, NF-κB, AMPK, and PPARγ, were assessed.
• Cellular reactive oxygen species (ROS) production and inflammatory cytokine secretion were measured.

Main Results:

• LC and Na2S supplementation reduced ROS production and increased phosphatidylinositol-3,4,5-trisphosphate (PIP3) levels in HG-exposed cells.
• Hydrogen sulfide (H2S) was identified as a key mediator of LC's effect on PIP3.
• Supplementation with LC and Na2S suppressed NF-κB phosphorylation and the secretion of pro-inflammatory cytokines (TNF-α, MCP-1, IL-8, IL-1β, IP-10).
• LC, Na2S, and PIP3 treatment upregulated AMPK phosphorylation and PPARγ expression in HG-exposed cells.

Conclusions:

• This study reveals a novel molecular mechanism where L-cysteine (LC) and hydrogen sulfide (H2S) supplementation mitigate oxidative stress and vascular inflammation in diabetes.
• The findings highlight the therapeutic potential of targeting the LC-H2S pathway to manage diabetic vascular complications.