Homocysteine induces metalloproteinase and shedding of beta-1 integrin in microvessel endothelial cells

Journal of Cellular Biochemistry
Suresh Shastry, Suresh C Tyagi

Abstract

Although studies have suggested microvessel endothelial cells (MVEC) activation and induction of matrix metalloproteinases (MMPs) by homocysteine (Hcy), the transduction mechanism leading to endothelial activation was unclear. We hypothesized that Hcy induced metalloproteinase and altered the levels of integrin in MVEC. MVEC from mouse brain were isolated and characterized by CD-31 (PECAM-1) FITC labeling. The MVEC were activated with different doses (6-40 microM) of Hcy. The cultured-conditioned-medium was analyzed for MMP activity by gelatin gel-zymography. TIMP-1, -4, beta-1 integrin, and a disintegrin and metalloproteinase-12 (ADAM-12) were quantified by Western blot analysis. We used MVEC in cell culture to study the effect of increasing concentrations of Hcy upon the secretion of various proteins into the culture medium. MMP-9, beta-1 integrin, ADAM-12, and TIMP-1 were found in increased concentrations in the culture medium of Hcy-treated cells whereas TIMP-4 was decreased. We have shown that purified TIMP-4 blocked the increase of beta-1 integrin shedding in Hcy-treated cells. Interestingly, our results suggest that TIMP-1 and TIMP-4 function antagonistically in Hcy-induced signaling pathways.

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Citations

May 19, 2007·Antioxidants & Redox Signaling·Utpal SenSuresh C Tyagi
Sep 11, 2010·Cardiovascular Diabetology·Paras K MishraSuresh C Tyagi
Apr 3, 2007·Proceedings of the National Academy of Sciences of the United States of America·Martine Cohen-SalmonChristine Petit
Dec 21, 2006·Archives of Physiology and Biochemistry·Dorothea RosenbergerSuresh C Tyagi
Dec 11, 2007·Clinical Chemistry and Laboratory Medicine : CCLM·Wolfgang HerrmannSuresh C Tyagi
Dec 23, 2015·Biochimica Et Biophysica Acta·Atticus H HainsworthDonna M Wilcock
Apr 12, 2005·Journal of Cardiovascular Pharmacology and Therapeutics·Suresh C TyagiIrving G Joshua
Mar 1, 2006·European Journal of Heart Failure·Markus HerrmannWolfgang Herrmann
Oct 28, 2005·American Journal of Physiology. Cell Physiology·Karni S MoshalSuresh C Tyagi
Feb 10, 2020·Clinical & Experimental Optometry : Journal of the Australian Optometrical Association·Mehmet YilmazHakan Türkön
Oct 13, 2010·Molecular and Cellular Biochemistry·Lamia RaafNathalie Janel
Nov 16, 2018·Frontiers in Aging Neuroscience·Brittani R PriceErica M Weekman
May 17, 2005·Journal of Cellular Physiology·Suresh ShastrySuresh C Tyagi

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