Effects of nitric oxide and antioxidants on advanced glycation end products-induced hypertrophic growth in human renal tubular cells.
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.
Huang
Jau-Shyang
JS
Department of Biological Science and Technology, Chung Hwa University of Medical Technology, 717 Tainan. jaushyang12@hotmail.com
Chuang
Lea-Yea
LY
Guh
Jinn-Yuh
JY
Huang
Yann-Jia
YJ
D000975:Antioxidants / Q000494:pharmacology*; D015153:Blotting, Western; D002460:Cell Line; D048429:Cell Size; D006152:Cyclic GMP / Q000378:metabolism; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism; D005353:Fibronectins / Q000096:biosynthesis; D005434:Flow Cytometry; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors / Q000633:toxicity*; D006801:Humans; D006984:Hypertrophy; D007684:Kidney Tubules / Q000166:cytology / Q000187:drug effects / Q000473:pathology*; D009569:Nitric Oxide / Q000096:biosynthesis / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D015689:Oncogene Protein p21(ras) / Q000096:biosynthesis; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors; D026423:S-Nitroso-N-Acetylpenicillamine / Q000494:pharmacology
D000975:Antioxidants; D005353:Fibronectins; D017127:Glycation End Products, Advanced; D020030:Nitric Oxide Donors; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D052247:Nitric Oxide Synthase Type II; D017869:Cyclic GMP-Dependent Protein Kinases; D015689:Oncogene Protein p21(ras); D006152:Cyclic GMP