Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.4.24.23 (
MMP
)
4,246
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Degradation of
myosin light chain 1
(
MLC1
) by matrix metalloproteinase 2 (MMP-2) during myocardial ischemia/reperfusion (I/R) has been demonstrated. However, the exact mechanisms controlling this process remain unknown. I/R increases the phosphorylation of
MLC1
, but the consequences of this modification are not known. We hypothesized that phosphorylation of
MLC1
plays an important role in its degradation by MMP-2. To examine this, isolated perfused rat hearts were subjected to 20 min global ischemia followed by 30 min of aerobic reperfusion. I/R increased phosphorylation of
MLC1
(as measured by mass spectrometry). When hearts were subjected to I/R in the presence of ML-7 (a myosin light-chain kinase inhibitor) or doxycycline (an
MMP
inhibitor), improved recovery of contractile function was observed compared to aerobic controls, and
MLC1
was protected from degradation. Enzyme kinetic studies revealed an increased affinity of MMP-2 for the phosphorylated form of
MLC1
compared to non-phosphorylated
MLC1
. We conclude that
MLC1
phosphorylation is an important mechanism controlling the intracellular action of MMP-2 and promoting degradation of
MLC1
. These results further support previous findings implicating post-translational modifications of contractile proteins as a key factor in the pathology of cardiac dysfunction during and following ischemia.
...
PMID:Ischemia/reperfusion-induced myosin light chain 1 phosphorylation increases its degradation by matrix metalloproteinase 2. 2256 71
