Cited by 18Cell death mechanisms and regulationIon Transport and Channel RegulationFOXO transcription factor regulation

SGK1 mediates the hypotonic protective effect against H2O2-induced apoptosis of rat basilar artery smooth muscle cells by inhibiting the FOXO3a/Bim signaling pathway

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Chen, Bao-yi, Huang, Cheng-cui, Lv, Xiao-fei, Zheng, Hua-qing, Zhang, Ya-juan, Sun, Lu, Wang, Guan-lei, Ma, Ming-ming +1 more·2020·Acta Pharmacologica Sinica

Abstract

Serum- and glucocorticoid-inducible kinease-1 (SGK1) is a serine/threonine kinase regulated by hypotonic stimuli, which is involved in regulation of cell cycle and apoptosis. Our previous study shows that activation of volume-regulated Cl- channels (VRCCs) protects rat basilar artery smooth muscle cells (BASMCs) against hydrogen peroxide (H 2 O 2)-induced apoptosis. In the present study, we investigated whether SGK1 was involved in the protective effect of VRCCs in BASMCs. We showed that hypotonic challenge significantly reduced H 2 O 2-induced apoptosis, and increased SGK1 phosphorylation, but did not affect SGK1 protein expression. The protective effect of hypotonic challenge against H 2 O 2-induced apoptosis was mediated through inhibiting mitochondria-dependent apoptotic pathway, evidenced by increased Bcl-2/Bax ratio, stabilizing mitochondrial membrane potential (MMP), decreased cytochrome c release from the mitochondria to the cytoplasm, and inhibition of the activation of caspase-9 and caspase-3. These protective effects of hypotonic challenge against H 2 O 2-induced apoptosis was diminished and enhanced, respectively, by SGK1 knockdown and overexpression. We further revealed that SGK1 activation significantly increased forkhead box O3a (FOXO3a) phosphorylation, and then inhibited the translocation of FOXO3a into nucleus and the subsequent expression of Bcl-2 interacting mediator of cell death (Bim). In conclusion, SGK1 mediates the protective effect of VRCCs against H 2 O 2-induced apoptosis in BASMCs via inhibiting FOXO3a/Bim signaling pathway. Our results provide compelling evidences that SGK1 is a critical link between VRCCs and apoptosis, and shed a new light on the treatment of vascular apoptosis-associated diseases, such as vascular remodeling, angiogenesis, and atherosclerosis.

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  • Amplification of SGK1 expression inhibits apoptosis in rat basilar artery smooth muscle cells through a mitochondrial-dependent intrinsic pathway.

    “amplification SGK1 expression inhibits apoptosis in rat basilar artery smooth muscle cells through a mitochondrial-dependent intrinsic pathway within these cells”

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Authors
Chen, B.-Y., Huang, C.-C., Lv, X.-F., Zheng, H.-Q., Zhang, Y.-J., Sun, L., Wang, G.-L., Ma, M.-M., & Guan, Y.-Y.
Affiliations
Sun Yat-sen University (CN)
Corresponding author
Guan, Yong-yuan
Venue
Acta Pharmacologica Sinica
Published
2020-03-05
Volume
41
Issue
8
Pages
1073-1084
ISSN
  • 0253-9756 (ISSN-L)
  • 1671-4083
  • 1745-7254
OpenAlex
W3010061535
Cited by
18
References
49
Citations by year
2026: 1 · 2025: 2 · 2024: 4 · 2023: 1 · 2022: 6 · 2021: 4
FWCI
0.89
Type
journal article
Language
en
Open access
Locations
  • Acta Pharmacologica Sinica (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Natural Science Foundation of China (81773721, 81773722)
  • Natural Science Foundation of Guangdong Province (2018A030310233)
  • Guangzhou Municipal Science and Technology Project
  • Fundamental Research Funds for the Central Universities
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › FOXO transcription factor regulation
Keywords
SGK1, hypotonic stress, volume-regulated chloride channels, hydrogen peroxide-induced apoptosis, FOXO3, building information modeling, mitochondrial apoptosis, cytochrome c release, mitochondrial membrane potential, caspase-9, caspase-3, Bcl-2/Bax ratio, vascular remodeling, atherosclerosis
MeSH terms
Forkhead Box Protein O3, Bcl-2-Like Protein 11, Serum-Glucocorticoid Regulated Kinases, Animals, Basilar Artery, Hydrogen Peroxide, Male, Osmotic Pressure, Signal Transduction, Down-Regulation, Rats, Sprague-Dawley, Apoptosis, Protein Serine-Threonine Kinases, Immediate-Early Proteins, Chloride Channels, Myocytes, Smooth Muscle

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