Nifedipine, a calcium channel blocker, inhibits advanced glycation end product (AGE)-elicited mesangial cell damage by suppressing AGE receptor (RAGE) expression via peroxisome proliferator-activated receptor-gamma activation.

Abstract

The interaction between advanced glycation end products (AGE) and their receptor RAGE mediates the progressive alteration in renal architecture and loss of renal function in diabetic nephropathy. Oxidative stress generation and inflammation also play a central role in diabetic nephropathy. This study investigated whether and how nifedipine, a calcium channel blocker (CCB), blocked the AGE-elicited mesangial cell damage in vitro. Nifedipine, but not amlodipine, a control CCB, down-regulated RAGE mRNA levels and subsequently reduced reactive oxygen species (ROS) generation in AGE-exposed mesangial cells. AGE increased mRNA levels of vascular cell adhesion molecule-1 (VCAM-1) and induced monocyte chemoattractant protein-1 (MCP-1) production in mesangial cells, both of which were prevented by the treatment with nifedipine, but not amlodipine. The beneficial effects of nifedipine on AGE-exposed mesangial cells were blocked by the simultaneous treatment of GW9662, an inhibitor of peroxisome proliferator-activated receptor-gamma (PPAR-gamma). Although nifedipine did not affect expression levels of PPAR-gamma, it increased the PPAR-gamma transcriptional activity in mesangial cells. Our present study provides a unique beneficial aspect of nifedipine on diabetic nephropathy; it could work as an anti-inflammatory agent against AGE by suppressing RAGE expression in cultured mesangial cells via PPAR-gamma activation.

• Authors: Takanori Matsui, Sho-ichi Yamagishi, Masayoshi Takeuchi, Seiji Ueda, Kei Fukami, Seiya Okuda
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 385 Issue 2 Pg. 269-72 (Jul 24 2009) ISSN: 1090-2104 [Electronic] United States
• PMID: 19460355 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 2-chloro-5-nitrobenzanilide
• Anilides
• CCL2 protein, human
• Calcium Channel Blockers
• Chemokine CCL2
• Glycation End Products, Advanced
• PPAR gamma
• Reactive Oxygen Species
• Receptor for Advanced Glycation End Products
• Receptors, Immunologic
• Nifedipine

Topics

• Anilides (pharmacology)
• Calcium Channel Blockers (pharmacology)
• Chemokine CCL2 (biosynthesis)
• Cytoprotection
• Glycation End Products, Advanced (metabolism)
• Humans
• Mesangial Cells (drug effects, metabolism)
• Nifedipine (pharmacology)
• PPAR gamma (agonists)
• Reactive Oxygen Species (metabolism)
• Receptor for Advanced Glycation End Products
• Receptors, Immunologic (antagonists & inhibitors)
• Transcription, Genetic