Abstract:
:Treatment of microsomes (preferably enriched with endoplasmic reticulum) isolated from bovine pulmonary artery smooth muscle tissue with the O2*- -generating system (hypoxanthine (HPX) plus xanthine oxidase (XO)), markedly stimulated matrix metalloproteinase-2 (MMP-2) activity and also enhanced Ca2+ ATPase activity and ATP-dependent Ca2+ uptake. Pretreatment with superoxide dismutase (SOD) and tissue inhibitor of metalloproteinase (TIMP-2) (50 microg ml(-1)), preserved the increase in MMP-2 activity, Ca2+ ATPase activity and also ATP-dependent Ca2+ uptake in the microsomes. In contrast, Na+-dependent Ca2+ uptake in the microsomes was found to be inhibited by the O2*- - generating system. Additionally, O2*- -induced inhibition of Na+-dependent Ca2+ uptake was reversed by SOD and TIMP-2 (50 microg ml(-1)). Electron microscopy revealed that treatment with the O2*- -generating system did not cause any noticeable damage to the microsomes. O2*- -induced changes in MMP-2 activity, ATP-dependent Ca2+ uptake and Na+-dependent Ca2+ uptake, were not reversed upon pretreatment of the microsomes with a low dose (5 microg ml(-1)) of TIMP-2 which, on the contrary, reversed MMP-2 (1 microg ml(-1))-mediated alteration on these parameters. The inhibition of Na+-dependent Ca2+ uptake by O2*- and MMP-2, overpowered the stimulation of ATP-dependent Ca2+ uptake in the microsomes. Treatment of TIMP-2 (5 microg ml(-1)) with the O2*- -generating system abolished the inhibitory effect of TIMP-2 (5 microg ml(-1)) on MMP-2 (1 microg ml(-1)) (measured by (14)C-gelatin degradation). Overall, the present study suggests that O2*- inactivated TIMP-2, the ambient inhibitor of MMP-2, leading to activation of the ambient proteinase, MMP-2, which subsequently stimulated Ca2+ ATPase activity and ATP-dependent Ca2+ uptake, but inhibited Na+-dependent Ca2+ uptake, resulting in a marked decrease in Ca2+ uptake in the smooth muscle microsomes.
journal_name
IUBMB Lifejournal_title
IUBMB lifeauthors
Mandal A,Chakraborti T,Das S,Ghosh B,Ghosh A,Chakraborti Sdoi
10.1080/1521654041000171335keywords:
subject
Has Abstractpub_date
2004-05-01 00:00:00pages
267-76issue
5eissn
1521-6543issn
1521-6551pii
UB83FHM8X1XB5YL7journal_volume
56pub_type
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