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Role of MMP-2 in inhibiting Na+ dependent Ca2+ uptake by H2O2 in microsomes isolated from pulmonary smooth muscle

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Abstract

Treatment of microsomes (preferentially enriched with endoplasmic reticulum) isolated from bovine pulmonary artery smooth muscle tissue with H2O2 (1 mM) markedly stimulated matrix metalloproteinase activity and also inhibited Na+ dependent Ca2+ uptake. Electron micrograph revealed that H2O2 (1 mM) does not cause any damage to the microsomes. MMP-2 and TIMP-2 were determined to be the ambient protease and corresponding antiprotease of the microsomes. Pretreatment with vitamin E (1 mM) and TIMP-2 (50 μg/ml) reversed the effect produced by H2O2 (1 mM) on Na+ dependent Ca2+ uptake in the microsomes. However, H2O2 (1 mM) caused changes in MMP-2 activity and Na+ dependent Ca2+ uptake were not reversed upon pretreatment of the microsomes with a low concentration of 5 μg/ml of TIMP-2 which otherwise reversed MMP-2 (1 μg/ml) mediated increase in 14C-gelatin degradation and inhibition of Na+ dependent Ca2+ uptake. Combined treatment of the microsomes with a low dose of MMP-2 (0.5 μg/ml) and H2O2 (0.5 mM) inhibited Na+ dependent Ca2+ uptake in the microsomes compared to the respective low dose of either of them. Direct treatment of TIMP-2 (5 μg/ml) with H2O2 (1 mM) abolished the inhibitory effect of the inhibitor on 14C-gelatinolytic activity elicited by 1 μg/ml of MMP-2. Thus, one of the mechanisms by which H2O2 activates MMP-2 could be due to inactivation of TIMP-2 by the oxidant. The resulting activation of MMP-2 subsequently inhibits Na+ dependent Ca2+ uptake in the microsomes. (Mol Cell Biochem 270: 79–87, 2005)

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Authors and Affiliations

  1. Department of Biochemistry and Biophysics, University of Kalyani, Kalyani, 741235, West Bengal, India

    Amritlal Mandal, Tapati Chakraborti, Rajdeep Choudhury, Biswarup Ghosh, Sudip Das & Sajal Chakraborti (Reader)

  2. Division of Electron Microscopy, National Institute of Cholera and Enteric Diseases (NICED), Kolkata, India

    Amar Nath Ghosh

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  1. Amritlal Mandal
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Mandal, A., Chakraborti, T., Choudhury, R. et al. Role of MMP-2 in inhibiting Na+ dependent Ca2+ uptake by H2O2 in microsomes isolated from pulmonary smooth muscle. Mol Cell Biochem 270, 79–87 (2005). https://doi.org/10.1007/s11010-005-5260-9

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