Homocysteine stimulates monocyte chemoattractant protein-1 expression in mesangial cells via NF-kappaB activation

Canadian Journal of Physiology and Pharmacology
Giselle T Y CheungKarmin O

Abstract

Hyperhomocysteinemia is regarded as an independent risk factor for cardiovascular disorders. Although renal dysfunction or failure is one of the important factors causing hyperhomocysteinemia, the role of homocysteine (Hcy) in the development of glomerulosclerosis is largely unknown. One of the key events in the pathogenesis of glomerulosclerosis is the infiltration of circulating monocytes into affected glomeruli. The objective of the present study was to investigate the effect of Hcy on the expression of monocyte chemoattractant protein-1 (MCP-1) in kidney mesangial cells and the mechanisms involved. Levels of MCP-1 and mRNA were significantly elevated in Hcy-treated rat mesangial cells. This increase was associated with activation of NF-kappaB as a result of increased phosphorylation of the inhibitor protein IkappaBalpha. Monocyte chemotactic activity in these cells was also enhanced. In addition, there was a significant elevation of superoxide anion produced by Hcy-treated cells, which preceded the increased phosphorylation of IkappaBalpha. Addition of superoxide dismutase or NF-kappaB inhibitors to the culture medium abolished Hcy-induced NF-kappaB activation and MCP-1 expression. Taken together, these results indicate tha...Continue Reading

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Citations

Oct 21, 2016·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Gregory J WeberUtpal Sen
Aug 26, 2014·Clinica Chimica Acta; International Journal of Clinical Chemistry·Wen-Jun PanZhi-Sheng Jiang
Mar 17, 2016·World Journal of Biological Chemistry·Violeta G TruscaAnca V Gafencu
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Mar 3, 2009·The FEBS Journal·Carole Brasse-LagnelAnnie Husson
Jun 26, 2020·Frontiers in Medicine·Yue ShangKarmin O

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