›› 2013, Vol. 33 ›› Issue (4): 385-.doi: 10.3969/j.issn.1674-8115.2013.04.001

• Original article (Basic research) •     Next Articles

Effect of (S)-3,5-dihydroxyphenylglycine on puromycin aminonucleoside-induced apoptosis of podocytes in vitro

LI Xiao-ying, GU Le-yi, NI Zhao-hui, LIANG Xin-yue, YAN Yu-cheng, QIAN Jia-qi   

  1. Department of Nephrology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200127, China
  • Online:2013-04-28 Published:2013-05-03
  • Supported by:

    National Natural Science Foundation of China, 30971363； Natural Science Foundation of Shanghai, 08ZR1413200； Shanghai Science and Technology Committee Foundation, 07JC14037, 10JC1410200

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Abstract:

Objective To investigate the effect of (S)-3,5-dihydroxyphenylglycine (DHPG), a selective metabotropic glutamate receptors (mGluR) 1 and 5 agonist, on aminonucleoside puromycin (PAN)induced podocyte apoptosis in vitro, and explore the possible mechanism. Methods Conditional immortalized mouse podocytes 5P12 were cultured in vitro, and were grouped based on different interventions. CCK-8, Western blotting, EIA, JC-1 staining and flow cytometry, immunofluorescence staining, TUNEL staining and confocal laser scanning microscopy were employed to examine the cell viability, expression of mGluR1/5 and activated cleaved caspase-3, cyclic adenosine monophosphate (cAMP) level, mitochondrial membrane potential, cAMP responsive element binding protein (CREB) and apoptosis of podocytes. Results Podocytes treated with DHPG generated cAMP and activated expression of CREB. DHPG inhibited PANinduced podocyte loss, cleaved caspase-3 upregulation, decrease of mitochondrial membrane potential and advanced apoptosis, which could be suppressed by selective antagonist of mGluR1/5 (AIDA), adenylate cyclase inhibitor (SQ22536) and RNA interference-mediated knockdown of mGluR1 or mGluR5. Conclusion DHPG can protect against PAN-induced apoptosis of podocytes, which may be associated with mGluR/cAMP signalling pathway.

Key words: metabotropic glutamate receptor 1, metabotropic glutamate receptor 5, podocyte, apoptosis, cyclic adenosine monophosphate