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: UNIPROT:P04179 (
MnSOD
)
2,777
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Vascular dysfunction is a common result of diabetes in humans. However, the mechanism underlying diabetic vascular dysfunction is not fully understood. Here in the present study, we showed that the
histone deacetylase 2
(
HDAC2
) promoted the endothelial dysfunction induced by diabetes. The expression and activity of
HDAC2
were up-regulated in vascular endothelial cells (ECs) from diabetic patients and mice. The expression of
HDAC2
was also increased by high glucose stress in isolated human ECs.
HDAC2
knockdown repressed the proliferation rate and promoted high glucose-induced apoptosis of ECs, which was associated with the activation of apoptotic pathways (Bcl-2, Caspase 3, and Bax). By contrast,
HDAC2
overexpression led to opposing results. Significantly, we observed that
HDAC2
regulated the accumulation of reactive oxygen species (ROS) induced by high glucose in ECs, which accounted for the effects of
HDAC2
on proliferation and apoptosis because antioxidants, N-acetyl-l-cysteine (NAC) or MnTBAP treatment blocked the effects of
HDAC2
on apoptosis of ECs under high glucose condition. Mechanism study revealed that
HDAC2
bound to the promoter of
MnSOD
and repressed the expression of
MnSOD
by regulating the level of acetylated H3K9 and H3K27, which led to the promotion of oxidative stress and contributed to the function of
HDAC2
in ECs under high glucose condition. Altogether, our evidence demonstrated that
HDAC2
-
MnSOD
signaling was critical in oxidative stress and proliferation as well as the survival of ECs under high glucose condition.
...
PMID:HADC regulates the diabetic vascular endothelial dysfunction by targetting MnSOD. 3021 47
