Calpain inhibitors exhibit matrix metalloproteinase-2 inhibitory activity.

Biochemical and Biophysical Research Communications
Mohammad A M AliRichard Schulz

Abstract

Matrix metalloproteinase (MMP)-2 is a zinc-dependent endopeptidase which, alongside its known extracellular actions, plays fundamental roles in oxidative stress-induced injury to the heart. Intracellular cleavage targets of MMP-2 selectively mediating this injury include the sarcomeric proteins troponin I, myosin light chain-1 and titin; some of these are also targeted by calpains. In myocardial ischemia and reperfusion injury, inhibitors of MMP-2 and some calpain inhibitors were shown to improve the recovery of contractile function. We hypothesized that the protective effects of calpain inhibitors may be due in part to their ability to inhibit MMP-2. Four calpain inhibitors (calpain inhibitor III, ALLM, ALLN, and PD-150606) were tested for their ability to inhibit MMP-2 in comparison to the selective MMP inhibitor ONO-4817. At 100 μM, all calpain inhibitors, except ALLM, showed significant inhibition of MMP-2 gelatinolytic activity. When assessed by the troponin I proteolysis assay, both ALLN and PD-150606, but neither ALLM nor calpain inhibitor III (at 20 μM), significantly inhibited MMP-2 activity. Using a fluorogenic MMP substrate peptide OmniMMP in a kinetic assay the rank order of IC(50) values against MMP-2 were: PD-1506...Continue Reading

References

Jun 25, 1996·Proceedings of the National Academy of Sciences of the United States of America·K K WangP Yuen
Apr 28, 1999·Journal of Cardiovascular Pharmacology·H IwamotoM Matsuzaki
Jun 17, 2000·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·A YamadaK Ogawa
Aug 23, 2001·Trends in Molecular Medicine·Y Huang, K K Wang
Sep 7, 2001·Current Opinion in Cell Biology·L J McCawley, L M Matrisian
Jun 15, 1962·Proceedings of the National Academy of Sciences of the United States of America·J GROSS, C M LAPIERE
Jun 1, 2005·Trends in Pharmacological Sciences·Pal PacherCsaba Szabó
Nov 30, 2006·Annual Review of Pharmacology and Toxicology·Richard Schulz
Jan 2, 2007·Biochemical and Biophysical Research Communications·Hiroshi OhnoKen-ichi Yoshida
Jun 2, 2007·Nature Reviews. Drug Discovery·Jialiang HuGhislain Opdenakker
Dec 7, 2007·The New England Journal of Medicine·Radhakrishnan Ramaraj
Jan 11, 2008·American Journal of Physiology. Cell Physiology·Dan ShanJohn C Chatham
Jul 22, 2009·Biochemical and Biophysical Research Communications·Adrian C NicolescuRichard Schulz
Aug 7, 2009·Cardiovascular Research·Arulmozhi D KandasamyRichard Schulz
Sep 8, 2009·American Journal of Physiology. Heart and Circulatory Physiology·Santhosh K ManiDhandapani Kuppuswamy
Jun 18, 2010·Canadian Journal of Physiology and Pharmacology·James S C GilchristGrant N Pierce
Sep 4, 2010·Critical Reviews in Biochemistry and Molecular Biology·Bénédicte Cauwe, Ghislain Opdenakker
Jan 4, 2012·Journal of Cellular Physiology·Mohammad A M AliRichard Schulz

❮ Previous
Next ❯

Citations

Jun 19, 2013·Biochemical Pharmacology·M M CastroR Schulz
Jan 19, 2013·Circulation Research·Susan F Steinberg
Sep 28, 2014·Journal of Molecular and Cellular Cardiology·Ashley DeCouxRichard Schulz
Oct 28, 2015·Pflügers Archiv : European journal of physiology·Lauriane Y M MichelRené J M Bindels
Aug 28, 2015·Heart Failure Reviews·George H KunkelSuresh C Tyagi
Apr 23, 2013·Biochimica Et Biophysica Acta·Valentina ParraSergio Lavandero
Sep 10, 2014·Biochimica Et Biophysica Acta·Kristin E LowRobert L Campbell
Nov 12, 2016·Nature Reviews. Drug Discovery·Yasuko OnoHiroyuki Sorimachi
May 2, 2017·Cardiovascular Research·Marcos PoncelasDavid Garcia-Dorado
Nov 23, 2016·The Journal of Biological Chemistry·Himakarnika AlluriBinu Tharakan
Jan 25, 2018·Circulation Research·Valentina ParraBeverly A Rothermel
Sep 12, 2019·Basic Research in Cardiology·Brandon Y H ChanRichard Schulz
Dec 12, 2012·Journal of Applied Physiology·Alison L MüllerNaranjan S Dhalla
May 6, 2014·American Journal of Physiology. Heart and Circulatory Physiology·Bruno BuchholzRicardo J Gelpi
Jul 25, 2021·International Journal of Molecular Sciences·Adeleye O Adewale, Young-Hoon Ahn

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cardiomyopathy

Cardiomyopathy is a disease of the heart muscle, that can lead to muscular or electrical dysfunction of the heart. It is often an irreversible disease that is associated with a poor prognosis. There are different causes and classifications of cardiomyopathies. Here are the latest discoveries pertaining to this disease.

Cardiovascular Disease Pathophysiology

Cardiovascular disease involves several different processes that contribute to the pathological mechanism, including hyperglycemia, inflammation, atherosclerosis, hypertension and more. Vasculature stability plays a critical role in the development of the disease. Discover the latest research on cardiovascular disease pathophysiology here.

Related Papers

Biochemical and Biophysical Research Communications
Adrian C NicolescuRichard Schulz
Dental Materials : Official Publication of the Academy of Dental Materials
Lorenzo BreschiDavid H Pashley
© 2021 Meta ULC. All rights reserved