title: Novel hydrogen sulfide-releasing compound, S-propargyl-cysteine, prevents STZ-induced diabetic nephropathy.
abstract: In this work, we demonstrated for the first time that S-propargyl-cysteine (SPRC, also named as ZYZ-802), a novel hydrogen sulfide (H2S)-releasing compound, had renoprotective effects on streptozotocin (STZ)-induced diabetic kidney injury. SPRC treatment significantly reduced the level of creatinine, kidney to body weight ratio and in particular, markedly decreased 24-h urine microalbuminuria excretion. SPRC suppressed the mRNA expression of fibronectin and type IV collagen. In vitro, SPRC inhibited mesangial cells over-proliferation and hypertrophy induced by high glucose. Additionally, SPRC attenuated inflammation in diabetic kidneys. SPRC also reduced transforming growth factor β1 (TGF-β1) signaling and expression of phosphorylated Smad3 (p-Smad3) pathway. Moreover, SPRC inhibited phosphorylation of ERK, p38 protein. Taken together, SPRC was demonstrated to be a potential therapeutic candidate to suppress diabetic nephropathy.
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Qian
authors.affiliation: Departments of Physiology and Pathophysiology, Shanghai College of Medicine, Fudan University, Shanghai, China.
authors.forename: Xinghui
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, China.
authors.forename: Fenfen
authors.initials: F
authors.lastname: Ma
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Luo
authors.affiliation: Departmentof Biological Sciences, National University of Singapore, Singapore.
authors.forename: Ruowen
authors.initials: R
authors.lastname: Ge
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, China; Departmentof Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. Electronic address: zhuyz@fudan.edu.cn.
authors.forename: Yizhun
authors.initials: Y
authors.lastname: Zhu
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D005109:Extracellular Matrix / Q000378:metabolism; D006862:Hydrogen Sulfide / Q000097:blood / Q000378:metabolism; D007668:Kidney / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D050527:Mesangial Cells / Q000166:cytology / Q000187:drug effects; D009393:Nephritis / Q000188:drug therapy / Q000473:pathology; D017207:Rats, Sprague-Dawley; D051900:Smad3 Protein / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000502:physiology
chemical_list: C556437:S-propargylcysteine; D051900:Smad3 Protein; C497787:Smad3 protein, rat; D053773:Transforming Growth Factor beta1; D003545:Cysteine; D006862:Hydrogen Sulfide
keywords: Albuminuria; Diabetic nephropathy; Extracellular matrix; Fibrosis; Mesangial cell; S-propargyl-cysteine