Inhibition of apoptotic signalling in spermine-treated vascular smooth muscle cells by a novel glutathione precursor.

Cell Biology International
Indrani Sinha-HikimKeith C Norris

Abstract

CKD (chronic kidney disease) is a public health problem, mediated by haemodynamic and non-haemodynamic events including oxidative stress. We investigated the effect of two GSH (glutathione) precursors, NAC (N-acetylcysteine) and cystine as the physiological carrier of cysteine in GSH with added selenomethionine (F1) in preventing spermine (uraemic toxin)-induced apoptosis in cultured human aortic VSMC (vascular smooth muscle cells). VSMCs exposed to spermine (15 microM) with or without antioxidants (doses 50, 100, 200 and 500 microg/ml) were assessed for apoptosis, JNK (c-Jun-NH2-terminal kinase) activation and iNOS (inducible nitric oxide synthase) induction and activation of intrinsic pathway signalling. Spermine exposure resulted in activation of JNK and iNOS induction and apoptosis. NAC and F1 (dose range 50-500 microg/ml) attenuated spermine-induced acceleration of VSMC apoptosis but only F1 (at 200 and 500 microg/ml) maintained spermine-induced apoptosis at control levels. Spermine-induced JNK activation was prevented by 200 microg/ml of both NAC and F1, while iNOS induction was blocked only by F1. Notably, the adverse effects of spermine on BAX/BCL-2 ratio, cytochrome c release and caspase activation was fully attenuated...Continue Reading

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Citations

Mar 23, 2011·Apoptosis : an International Journal on Programmed Cell Death·Indrani Sinha-HikimAmiya P Sinha-Hikim
Jul 2, 2010·American Journal of Physiology. Cell Physiology·Indrani Sinha-HikimKeith C Norris
Mar 6, 2013·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Indrani Sinha-HikimKeith C Norris
May 17, 2011·Experimental and Molecular Pathology·Indrani Sinha-HikimKeith C Norris
Oct 21, 2016·Renal Failure·Kunal K Sindhu

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