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dc.contributor.authorPodsawee Mongkolpathumraten_US
dc.contributor.authorAnusak Kijtawornraten_US
dc.contributor.authorEukote Suwanen_US
dc.contributor.authorSasimanas Unajaken_US
dc.contributor.authorAussara Panyaen_US
dc.contributor.authorTonapha Pusadeeen_US
dc.contributor.authorSarawut Kumphuneen_US
dc.description.abstractInhibition of proteases shows therapeutic potential. Our previous studies demonstrated the cardioprotection by the Secretory Leukocyte Protease Inhibitor (SLPI) against myocardial ischaemia/reperfusion (I/R) injury. However, it is unclear whether the cardioprotective effect of SLPI seen in our previous works is due to the inhibition of protease enzymes. Several studies demonstrate that the anti-protease independent activity of SLPI could provide therapeutic benefits. Here, we show for the first time that recombinant protein of anti-protease deficient mutant SLPI (L72K, M73G, L74G) (mt-SLPI) could significantly reduce cell death and intracellular reactive oxygen species (ROS) production against an in vitro simulated I/R injury. Furthermore, post-ischaemic treatment of mt-SLPI is found to significantly reduce infarct size and cardiac biomarkers lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) activity, improve cardiac functions, attenuate I/R induced-p38 MAPK phosphorylation, and reduce apoptotic regulatory protein levels, including Bax, cleaved-Caspase-3 and total Capase-8, in rats subjected to an in vivo I/R injury. Additionally, the beneficial effect of mt-SLPI was not significantly different from the wildtype (wt-SLPI). In summary, SLPI could provide cardioprotection without anti-protease activity, which could be more clinically beneficial in terms of providing cardioprotection without interfering with basal serine protease activity.en_US
dc.subjectBiochemistry, Genetics and Molecular Biologyen_US
dc.titleAnti-Protease Activity Deficient Secretory Leukocyte Protease Inhibitor (SLPI) Exerts Cardioprotective Effect against Myocardial Ischaemia/Reperfusionen_US
article.volume10en_US Universityen_US Universityen_US Universityen_US Mai Universityen_US
Appears in Collections:CMUL: Journal Articles

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