Journal article
Apurinic/apyrimidinic endonuclease 1 inhibits protein kinase C-mediated p66shc phosphorylation and vasoconstriction
Cardiovascular research, Vol.91(3), pp.502-509
08/01/2011
DOI: 10.1093/cvr/cvr095
PMCID: PMC3139447
PMID: 21467074
Abstract
Aims
Phosphorylation of the adaptor protein p66shc is essential for p66shc-mediated oxidative stress. We investigated the role of the reducing protein/DNA repair enzyme apurinic/apyrimidinic endonuclease1 (APE1) in modulating protein kinase CβII (PKCβII)-mediated p66shc phosphorylation in cultured endothelial cells and PKC-mediated vasoconstriction of arteries.
Methods and results
Oxidized low-density lipoprotein (oxLDL)induced p66shc phosphorylation at serine 36 residue and PKCβII phosphorylation in mouse endothelial cells. Adenoviral overexpression of APE1 resulted in reduction of oxLDL-induced p66shc and PKCβII phosphorylation. Phorbol 12-myristate 13-acetate (PMA), which stimulates PKCs, induced p66shc phosphorylation and this was inhibited by a selective PKCβII inhibitor. Adenoviral overexpression of PKCβII also increased p66shc phosphorylation. Overexpression of APE1 suppressed PMA-induced p66shc phosphorylation. Moreover, PMA-induced p66shc phosphorylation was augmented in cells in which APE1 was knocked down. PMA increased cytoplasmic APE1 expression, compared with the basal condition, suggesting the role of cytoplasmic APE1 against p66shc phosphorylation. Finally, vasoconstriction induced by phorbol-12,13, dibutylrate, another PKC agonist, was partially inhibited by transduction of Tat-APE1 into arteries.
Conclusion
APE1 suppresses oxLDL-induced p66shc activation in endothelial cells by inhibiting PKCβII-mediated serine phosphorylation of p66shc, and mitigates vasoconstriction induced by activation of PKC.
Details
- Title: Subtitle
- Apurinic/apyrimidinic endonuclease 1 inhibits protein kinase C-mediated p66shc phosphorylation and vasoconstriction
- Creators
- Sang Ki Lee - 1 Infection Signaling Network Research Center, Research Institute of Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University, 6 Munhwa-dong, Jung-gu, Daejeon 301-131, KoreaJae In Chung - 1 Infection Signaling Network Research Center, Research Institute of Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University, 6 Munhwa-dong, Jung-gu, Daejeon 301-131, KoreaMyoung Soo Park - 1 Infection Signaling Network Research Center, Research Institute of Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University, 6 Munhwa-dong, Jung-gu, Daejeon 301-131, KoreaHee Kyoung Joo - 1 Infection Signaling Network Research Center, Research Institute of Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University, 6 Munhwa-dong, Jung-gu, Daejeon 301-131, KoreaEun Ji Lee - 1 Infection Signaling Network Research Center, Research Institute of Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University, 6 Munhwa-dong, Jung-gu, Daejeon 301-131, KoreaEun Jung Cho - 1 Infection Signaling Network Research Center, Research Institute of Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University, 6 Munhwa-dong, Jung-gu, Daejeon 301-131, KoreaJin Bong Park - 1 Infection Signaling Network Research Center, Research Institute of Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University, 6 Munhwa-dong, Jung-gu, Daejeon 301-131, KoreaSungwoo Ryoo - 2 Department of Biological Sciences, Kangwon National University, Chuncheon 200-701, KoreaKaikobad Irani - 3 Cardiovascular Institute, Department of Medicine, Vascular Medicine Institute, and Department of Pharmacology and Chemical Biology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USAByeong Hwa Jeon - 1 Infection Signaling Network Research Center, Research Institute of Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University, 6 Munhwa-dong, Jung-gu, Daejeon 301-131, Korea
- Resource Type
- Journal article
- Publication Details
- Cardiovascular research, Vol.91(3), pp.502-509
- Publisher
- Oxford University Press
- DOI
- 10.1093/cvr/cvr095
- PMID
- 21467074
- PMCID
- PMC3139447
- ISSN
- 0008-6363
- eISSN
- 1755-3245
- Language
- English
- Date published
- 08/01/2011
- Academic Unit
- Cardiovascular Medicine; Radiation Oncology; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
- Record Identifier
- 9984047606102771
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