Cordycepin Protects Podocytes from Injury Mediated by Complements Complex C5b-9

HONG Tao, CUI Lu-ke, WEN Ji. et al

Abstract

To explore the protective effect of Cordycepin (3’-deoxyadenosine), a bioactive compound of Cordyceps Sinensis, on injury of podocytes. Methods C5b-9-induced podocyte injury was used as a model of membranous nephropathy \in vitro. This model was established using mouse podocyte cell line——MPC5. Cordycepin was given as an intervention. Ultra-micro morphological changes were observed by electron microscope. F-actin cytoskeleton and expression of nephrin were observed by fluorescence microscope. The phosphorylation of mitogen-activated protein kinase (MAPK) was measured by Western blot. Results Stimulated by C5b-9 for 3 h, MPC5 showed secondary foot processes, with cytoskeleton structure damaged, nephrin relocated from the cell surface to the cytoplasm, and cell signal pathway-p38, JNK and ERK activated. Cordycepin protected foot processes and cytoskeleton structures of podocytes, suppressed the redistribution of nephrin, and inhibited p38/JNK action. Conclusion Cordycepin can protect podocyte from C5b-9-induced injury partly through inhibiting the activation of p38/JNK signaling pathway.

 

Keywords: Cordycepin, Podocyte, Complement complex, Membranous nephropathy, Mitogen-activated protein kinase 

 

Full Text:

PDF


References


Cybulsky AV. Membranous nephropathy. Contrib Nephrol, 2011;169:107-125. doi: 10.1159/000313948. Epub 2011 Jan 20.

Morgan BP. Effects of the membrane attack complex of complement on nucleated cells. Curr Top Microbiol Immunol, 1992;178:115-140.

Cybulsky AV, Papillon J, McTavish AJ. Complement activates phospholipases and protein kinases in glomerular epithelial cells. Kidney Int, 1998;54(2) :360-372.

Aoudjit L, Stanciu M, Li H, et al. P38 mitogen-activated protein kinase protects glomerular epithelial cells from complement-mediated cell injury. Am J Physiol Renal Physiol, 2003;285(4); F765-F774.

Tsui CC, Shankland SJ, Pierchala BA. Glial ell line-derived neurotrophic factor and its receptor ret is a novel ligand- receptor complex critical for survival response during podocyte injury. J Am Soc Nephrol.2006; 17(6): 1543-1552.

Takano T, Cybulsky AV, Yang X. et al. Complement C5b-9 induces cyclooxygenase-2 gene transcription in glomerular epithelial cells. Am J Physiol Renal Physiol, 2001; 281 ( 5) : F841-F850.

Peng H, Takano T, Papillon J. et al. Complement activates the c-Jun N-terminal kinase/stress-activated protein kinase in glomerular epithelial cells. J Immunol«2002; 169(5):2594- 2601.

Topham PS, Haydar SA. Kuphal R. et al. Complement- mediated injury reversibly disrupts glomerular epithelial cell actin micro-filaments and focal adhesions. Kidney Int,1999;55 (5):1763-1775.

Saran AM. Yuan H, Takeuchi E, et al. Complement mediates nephrin redistribution and actin dissociation in experimental membranous nephropathy. Kidney Int,2003;64(6):2072- 2078.

Schieppati A, Perna A, Zamora J, et al. Immunosuppressive treatment for idiopathic membranous nephropathy in adults with nephritic syndrome. Cochrane Database Syst Rev, 2004; 18(4) :CD004293.

Mathew PA, Ellis LK, Studzinski GP. Enhanced messenger RNA stability and differentiation of HL 60 cells treated with 1, 25 dihydroxy vitamin D3 and cordycepin. J Cell Physiol, 1989; 140(2):212-218.

Jeong JW, Jin CY, Kim GY, et al. Anti-inflammatory effects of cordycepin via suppression of inflammatory mediators in BV2 microglial cells. Int Immunopharmacol, 2010; 10 ( 12): 1580- 1586.

Kim HO, Sh rest ha B. Lim SY, et al. Cordycepin inhibits lipopolysaccharide-induced inflammation by the suppression of NF-kappa В through Akt and p38 inhibition in RAW 264. 7 macrophage cells. Eur J Pharmacol.2006 ; 18(2-3); 192-197.

Rao YK. Fang SH, Wu WS, et al. Constituents isolated from Cordyceps militaris suppress enhanced inflammatory mediator’s production and human cancer cell proliferation. J Ethnopharmacol'2010; 131(2);363-367.

Baik JS. К won HY. Kim KS, et al. Cordycepin induces apoptosis in human neuroblastoma SK-N-BE ( 2 )-C and melanoma SK-MEL-2 cells. India J Biochem Biophys, 2012; 49 (2):86-91.

Choi S, Lim MH, Kim KM, et al. Cordycepin-induced apoptosis and autophagy in breast cancer cells are independent of the estrogen receptor. Toxicol Appl Pharmacol, 2011; 257 (2):165-173.


Refbacks

  • There are currently no refbacks.