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:2.7.11.25 (
MEKK1
)
1,856
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
MEKK1
is a ubiquitously expressed mitogen activated protein kinase that is involved in tissue remodeling in a variety of settings including carotid artery blood flow cessation, wound healing, and breast adenocarcinoma intravasation. Here, we have tested the function of
MEKK1
in genetic hypertrophic cardiomyopathy (HCM).
MEKK1
was genetically deleted in C57Bl6/J mice expressing a mutant alpha-myosin heavy chain (HCM-
MEKK1
(-/-)). The absence of
MEKK1
in HCM resulted in a more pronounced hypertrophy when compared to HCM mice with the
MEKK1
gene intact without further increases in atrial natriuretic factor and beta-myosin heavy chain (MyHC) expression and fibrosis. Since
MEKK1
is required for the induction of several tissue proteases, we tested the hypothesis that cardiac enlargement of HCM-
MEKK1
(-/-) mice was due to altered expression of urokinase-type plasminogen activator (uPA), JunB, matrix-metalloproteinase (MMP), and tissue inhibitors of MMPs (TIMPs). Because of its role in preventing apoptosis, we also tested the loss of
MEKK1
on apoptotic mediators Bcl-2, cytochrome C, caspase-9, and caspase-3. uPA expression was decreased while JunB, MMP-9, caspase-9, and caspase-3 activities were elevated in HCM-
MEKK1
(-/-) hearts when compared to
MEKK1
(-/-), wild-type (WT), and HCM mice. Bcl-2 and
Cyt
C expression was elevated only in HCM mice. We conclude that the absence of
MEKK1
induces a more pronounced cardiac hypertrophy to HCM through altered expression of proteases implicated in cardiac remodeling and increased apoptosis.
...
PMID:The role of MEKK1 in hypertrophic cardiomyopathy. 2071 46
