Effects of Nitric Oxide and Antioxidants on Advanced Glycation End Products-Induced Hypertrophic Growth in Human Renal Tubular Cells | Zendy

JauShyang Huang | Zendy; LeaYea Chuang | Zendy; JinnYuh Guh | Zendy; Yann-Jia Huang | Zendy

Open Access

Effects of Nitric Oxide and Antioxidants on Advanced Glycation End Products-Induced Hypertrophic Growth in Human Renal Tubular Cells

Author(s) -

JauShyang Huang,

LeaYea Chuang,

JinnYuh Guh,

Yann-Jia Huang

Publication year - 2009

Publication title -

toxicological sciences

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 1.352

H-Index - 183

eISSN - 1096-6080

pISSN - 1096-0929

DOI - 10.1093/toxsci/kfp134

Subject(s) - nitric oxide , glycation , endocrinology , medicine , taurine , sodium nitroprusside , chemistry , rage (emotion) , snap , cgmp dependent protein kinase , protein kinase a , nitric oxide synthase , advanced glycation end product , reactive oxygen species , kinase , biochemistry , biology , diabetes mellitus , mitogen activated protein kinase kinase , computer graphics (images) , amino acid , neuroscience , computer science

The accumulation of advanced glycation end products (AGE) is a key mediator of renal tubular hypertrophy in diabetic nephropathy (DN). Reactive oxygen species and nitric oxide (NO) were involved in the progression of DN. In this study, the molecular mechanisms of NO and antioxidants responsible for inhibition of AGE-induced renal tubular hypertrophy were examined. We found that AGE (but not nonglycated bovine serum albumin) significantly suppressed the NO/cGMP/PKG signaling in human renal proximal tubular cells. NO donors S-nitroso-N-acetylpenicillamine (SNAP)/sodium nitroprusside (SNP) and antioxidants N-acetylcysteine (NAC)/taurine treatments significantly attenuated AGE-inhibited NO production, cGMP synthesis, and inducible NO synthase/cGMP-dependent protein kinase (PKG) activation. Moreover, AGE-induced extracellular signal-regulated kinase/c-Jun N-terminal kinase/p38 mitogen-activated protein kinase activation was markedly blocked by antireceptor for AGE (RAGE), SNAP, SNP, NAC, and taurine. The abilities of NO and antioxidants to inhibit AGE/RAGE-induced hypertrophic growth were verified by the observation that SNAP, SNP, NAC, and taurine inhibited fibronectin, p21(Waf1/Cip1), and RAGE expression. Therefore, antioxidants significantly attenuated AGE/RAGE-enhanced cellular hypertrophy partly through induction of the NO/cGMP/PKG signaling.

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