Inhibition of Nap>+p>/Cap>2+p> exchanger by peroxynitrite in microsomes of pulmonary smooth muscle: role of matrix metalloproteinase-2

详细信息	查看全文 | 推荐本文 |

• 作者：Chakraborti ; Sajal ; Mandal ; Amritlal ; Das ; Sudip ; Chakraborti ; Tapati
• 关键词：Oxidant ; Superoxide ; Nitric oxide ; Peroxynitrite ; Antioxidant ; Superoxide dismutase ; Matrix metalloproteinase-2 ; Tissue inhibitor of metalloproteinase-2 ; Microsome ; Pulmonary artery smooth muscle ; Cap>2+p>ATPase ; ATP-dependent Cap>2+p> uptak
• 刊名：Biochimica et Biophysica Acta (BBA)/General Subjects
• 出版年：2004
• 期刊代码：16_03044165
• 类别：bio
• 出版时间：March 17, 2004
• 卷：1671
• 期：1-3
• 页码：70-78
• 文件大小：216 K

摘要

Treatment of bovine pulmonary artery smooth muscle microsomes with peroxynitrite (ONOOp>−p>) (100 μM) markedly stimulated matrix metalloproteinase-2 (MMP-2) activity and also enhanced Cap>2+p>ATPase activity and ATP-dependent Cap>2+p> uptake. Pretreatment of the microsomes with vitamin E (1 mM) and TIMP-2 (50μg/ml) preserved the increase in MMP-2 activity, Cap>2+p>ATPase activity and also ATP-dependent Cap>2+p> uptake in the microsomes. In contrast, Nap>+p>-dependent Cap>2+p> uptake in the microsomes was inhibited by ONOOp>−p> and this was found to be reversed by vitamin E (1 mM) and TIMP-2 (50 μg/ml). However, changes caused by ONOOp>−p> in MMP-2 activity, ATP-dependent Cap>2+p> uptake and Nap>+p>-dependent Cap>2+p> uptake were not reversed upon pretreatment of the microsomes with a low concentration of 5 μg/ml of TIMP-2 which, on the contrary, reversed MMP-2 (1 μg/ml)-mediated alteration on these parameters. The inhibition of Nap>+p>-dependent Cap>2+p> uptake by ONOOp>−p> and MMP-2 overpowered the stimulation of ATP-dependent Cap>2+p> uptake in the microsomes. Treatment with ONOOp>−p> abolished the inhibitory effect of TIMP-2 (5 μg/ml) on MMP-2 (1 μg/ml) causing p>14p>C-gelatin degradation. Overall, the present study suggests that ONOOp>−p> inactivated TIMP-2, the ambient inhibitor of MMP-2, leading to activation of the ambient proteinase, MMP-2, and subsequently stimulated Cap>2+p>ATPase activity and ATP-dependent Cap>2+p> uptake, but inhibited Nap>+p>-dependent Cap>2+p> uptake, resulting in a marked decrease in Cap>2+p> uptake in microsomes of bovine pulmonary artery smooth muscle.