Protective effects of N-acetylcysteine amide (NACA) on gentamicin-induced apoptosis in LLC-PK1 cells

Autor:	Gianni Celsi, Katarina Carlsson, Xuezhong Gong, Svante Norgren
Rok vydání:	2012
Předmět:	MAPK/ERK pathway Cell Survival Swine p38 mitogen-activated protein kinases Poly ADP ribose polymerase Blotting Western Nitric Oxide Synthase Type II Apoptosis Critical Care and Intensive Care Medicine Polymerase Chain Reaction p38 Mitogen-Activated Protein Kinases Nephrotoxicity Animals Protein kinase A Cells Cultured bcl-2-Associated X Protein biology NF-kappa B General Medicine DNA Free Radical Scavengers Acute Kidney Injury Flow Cytometry Molecular biology Acetylcysteine Nitric oxide synthase Disease Models Animal NACA Gene Expression Regulation Proto-Oncogene Proteins c-bcl-2 Nephrology biology.protein LLC-PK1 Cells Gentamicins Signal Transduction
Zdroj:	Renal failure. 34(4)
ISSN:	1525-6049
Popis:	Apoptosis plays a critical role in the pathogenesis of gentamicin (Gen)-induced nephrotoxicity. However, the underlying molecular mechanisms still remain unclear. In this study, we addressed the role of p38 mitogen-activated protein kinase (MAPK)/inducible nitric oxide synthase (iNOS) signaling pathway in Gen-induced nephrotoxicity and evaluated the protective effect of the free-radical scavenger N-acetylcysteine amide (NACA).Pig kidney epithelial cells (LLC-PK1) cells were exposed to Gen for variable times and doses. Cytotoxicity was assessed by morphology and by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Protein expression was assessed by Western blotting.Exposure to Gen-induced apoptosis in a dose-dependent and time-dependent manner was assessed by DNA content analysis and poly ADP ribose polymerase (PARP) cleavage. Gen caused increased phosphorylation of p38 MAPK and induction of iNOS. This was accompanied by a significant upregulation of Bax and nuclear factor κB (NF-κB) and a downregulation of Bcl-2 expression. Pretreatment with SB203580, aminoguanidine (AG), and NACA inhibited apoptosis. Furthermore, pretreatment with SB203580 and NACA not only attenuated the pro-apoptotic effect of Gen, but also significantly reversed its effects on p38 MAPK phosphorylation and iNOS induction. The Gen-induced effects on Bcl-2, Bax, and NF-κB expression were also reversed by SB203580, AG, and NACA.In conclusion, NACA can attenuate Gen-induced apoptotic injury in LLC-PK1 cells through inhibiting p38 MAPK/iNOS signaling pathway.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::52e39ca3f98e05461d60163e3025d941 https://pubmed.ncbi.nlm.nih.gov/22486232 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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