Dataset Information

Overexpression of steroid receptor coactivators alleviates hyperglycemia-induced endothelial cell injury in rats through activating the PI3K/Akt pathway.

ABSTRACT: Hyperglycemia is a major factor in vascular endothelial injury that finally leads to a cardiovascular event. Steroid receptor coactivators (SRCs) are a group of non-DNA binding proteins that induce structural changes in steroid receptors (nuclear receptors) critical for transcriptional activation. SRCs, namely, SRC-1, SRC-2, and SRC-3, are implicated in the regulation of vascular homeostasis. In this study we investigate the role of SRCs in hyperglycemia-induced endothelial injury. Aortic endothelial cells were prepared from normal and diabetic rats, respectively. Diabetic rats were prepared by injection of streptozotocin (50?mg/kg, i.p.). The expression levels of SRC-1 and SRC-3 were significantly decreased in endothelial cells from the diabetic rats. Similar phenomenon was also observed in aortic endothelial cells from the normal rats treated with a high glucose (25?mM) for 4?h or 8?h. The expression levels of SRC-2 were little affected by hyperglycemia. Overexpression of SRC-1 and SRC-3 in high glucose-treated endothelial cells significantly increased the cell viability, suspended cell senescence, and inhibited cell apoptosis compared with the control cells. We further showed that overexpression of SRC-1 and SRC-3 markedly suppressed endothelial injury through restoring nitric oxide production, upregulating the expression of antioxidant enzymes (SOD, GPX, and CAT), and activating the PI3K/Akt pathway. The beneficial effects of SRC-1 and SRC-3 overexpression were blocked by treatment with the PI3K inhibitor LY294002 (10?mM) or with the Akt inhibitor MK-2206 (100?nM). In conclusion, hyperglycemia decreased SRC-1 and SRC-3 expression levels in rat aortic endothelial cells. SRC-1 and SRC-3 overexpression might protect against endothelial injury via inhibition of oxidative stress and activation of PI3K/Akt pathway.

SUBMITTER: Quan XJ

PROVIDER: S-EPMC6786429 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Overexpression of steroid receptor coactivators alleviates hyperglycemia-induced endothelial cell injury in rats through activating the PI3K/Akt pathway.

Quan Xiao-Juan XJ Liang Chun-Lian CL Sun Ming-Zhu MZ Zhang Lin L Li Xiu-Li XL

Acta pharmacologica Sinica 20180808 5

Hyperglycemia is a major factor in vascular endothelial injury that finally leads to a cardiovascular event. Steroid receptor coactivators (SRCs) are a group of non-DNA binding proteins that induce structural changes in steroid receptors (nuclear receptors) critical for transcriptional activation. SRCs, namely, SRC-1, SRC-2, and SRC-3, are implicated in the regulation of vascular homeostasis. In this study we investigate the role of SRCs in hyperglycemia-induced endothelial injury. Aortic endoth ...[more]

PMID: 30089865

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Dataset Information

Overexpression of steroid receptor coactivators alleviates hyperglycemia-induced endothelial cell injury in rats through activating the PI3K/Akt pathway.

Publications

Overexpression of steroid receptor coactivators alleviates hyperglycemia-induced endothelial cell injury in rats through activating the PI3K/Akt pathway.

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