Hydrogen Sulfide Inhibits High Glucose-induced Matrix Protein Synthesis by Activating AMP-activated Protein Kinase in Renal Epithelial Cells

Tadalafil Integrates Nitric Oxide-Hydrogen Sulfide Signaling to Inhibit High Glucose-induced Matrix Protein Synthesis in Podocytes

“…WT-1-positive (a podocyte marker) clonal cell lines were obtained by the limited dilution method and propagated (25). For this study, podocytes were grown in RPMI 1640 medium containing 7% FBS, 5 mM glucose, 100 units/ml penicillin, 100 g/ml streptomycin, 2 mM glutamine, and 50 units/ml recombinant mouse ␥-interferon (Gibco) on collagen I (BD Biosciences)-coated plates at 33°C, and differentiation was induced as described previously (12,25). To study the effects of high glucose, medium glucose was increased to 30 mM; equimolar 5 mM glucose ϩ 25 mM mannitol served as an osmotic control.…”

“…Mice lacking cystathionine ␥-lyase (CSE), an enzyme that synthesizes H 2 S, have high blood pressure that is ameliorated by sodium hydrosulfide, an H 2 S donor (14). We have recently reported that H 2 S inhibits high glucose-induced synthesis of proteins including extracellular matrix proteins in kidney epithelial cells (12). The mechanism involves activation of AMPK followed by inhibition of mTORC1 and events in mRNA translation culminating in inhibition of high glucose-induced matrix protein synthesis.…”

“…The mechanism involves activation of AMPK followed by inhibition of mTORC1 and events in mRNA translation culminating in inhibition of high glucose-induced matrix protein synthesis. H 2 S is generated in the kidney by cystathionine ␤-synthase, CSE, and, 3-mercaptopyruvate sulfurtransferase (12,(15)(16)(17). The content of cystathionine ␤-synthase and CSE is decreased in the kidney cortex of mice with type 1 or type 2 diabetes, and sodium hydrosulfide, an H 2 S donor, ameliorates diabetes-induced kidney injury (12,18,19).…”

“…There is a growing interest in other agents that stimulate AMPK. Recent investigations have shown that hydrogen sulfide (H 2 S) activates AMPK in kidney cells (12). H 2 S is constitutively synthesized in several tissues in mammals.…”

Regulation of Cellular Redox Signaling by Matricellular Proteins in Vascular Biology, Immunology, and Cancer

“…H 2 S inhibited glucose-induced laminin c1 synthesis in mouse podocytes and kidney proximal tubular epithelial cells via the mammalian target of rapamycin complex 1 (mTORC1)-AMP kinase pathway (131). CBS and CSE expression was significantly reduced in mice with type 1 or type 2 diabetes.…”