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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 저널정보
- 대한약리학회 The Korean Journal of Physiology & Pharmacology The Korean Journal of Physiology & Pharmacology 제21권 제4호
- 발행연도
- 2017.7
- 수록면
- 377 - 384 (8page)
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Activation of protein kinase C (PKC) is closely linked with endothelial dysfunction. However, the effect of PKCβII on endothelial dysfunction has not been characterized in cultured endothelial cells. Here, using adenoviral PKCβII gene transfer and pharmacological inhibitors, the role of PKCβII on endothelial dysfucntion was investigated in cultured endothelial cells. Phorbol 12-myristate 13-acetate (PMA) increased reactive oxygen species (ROS), p66shc phosphorylation, intracellular adhesion molecule-1, and monocyte adhesion, which were inhibited by PKCβi (10 nM), a selective inhibitor of PKCβII. PMA increased the phosphorylation of CREB and manganese superoxide dismutase (MnSOD), which were also inhibited by PKCβi.
Gene silencing of CREB inhibited PMA-induced MnSOD expression, suggesting that CREB plays a key role in MnSOD expression. Gene silencing of PKCβII inhibited PMA-induced mitochondrial ROS, MnSOD, and ICAM-1 expression. In contrast, overexpression of PKCβII using adenoviral PKCβII increased mitochondrial ROS, MnSOD, ICAM-1, and p66shc phosphorylation in cultured endothelial cells. Finally, PKCβII-induced ICAM-1 expression was inhibited by Mito-TEMPO, a mitochondrial ROS scavenger, suggesting the involvement of mitochondrial ROS in PKC-induced vascular inflammation. Taken together, the results suggest that PKCβII plays an important role in PMA-induced endothelial dysfunction, and that the inhibition of PKCβII-dependent p66shc signaling acts as a therapeutic target for vascular inflammatory diseases.
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참고문헌 (38)
참고문헌 신청
Giovannini C / 2002 / Mitochondria hyperpolarization is an early event in oxidized low-density lipoprotein-induced apoptosis in Caco-2intestinal cells / FEBS Lett 523:200~206
Munusamy S / 2009 / Mitochondrial superoxide plays a crucial role in the development of mitochondrial dysfunction during high glucose exposure in rat renal proximal tubular cells / Free Radic Biol Med 46:1149~1157
Sommer SP / 2011 / Ischemia-reperfusion injury-induced pulmonary mitochondrial damage / J Heart Lung Transplant 30:811~818
Chen KH / 1999 / Mitochondrial glutathione modulates TNF-alpha-induced endothelial cell dysfunction / Free Radic Biol Med 27:100~109
Zinovkin RA / 2014 / Role of mitochondrial reactive oxygen species in age-related inflammatory activation of endothelium / Aging(Albany NY) 6:661~674
Munusamy S / 2009 / Mitochondrial superoxide plays a crucial role in the development of mitochondrial dysfunction during high glucose exposure in rat renal proximal tubular cells / Free Radic Biol Med 46:1149~1157
Sommer SP / 2011 / Ischemia-reperfusion injury-induced pulmonary mitochondrial damage / J Heart Lung Transplant 30:811~818
Chen KH / 1999 / Mitochondrial glutathione modulates TNF-alpha-induced endothelial cell dysfunction / Free Radic Biol Med 27:100~109
Zinovkin RA / 2014 / Role of mitochondrial reactive oxygen species in age-related inflammatory activation of endothelium / Aging(Albany NY) 6:661~674
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