Roles of ROS and PKC-βII in ionizing radiation-induced eNOS activation in human vascular endothelial cells

Kimimasa Sakata, Takashi Kondo, Natsumi Mizuno, Miki Shoji, Hironobu Yasui, Tohru Yamamori, Osamu Inanami, Hiroki Yokoo, Naoki Yoshimura, Yuichi Hattori

研究成果: Article査読

18 被引用数 (Scopus)

抄録

Vascular endothelial cells can absorb higher radiation doses than any other tissue in the body, and post-radiation impaired endothelial nitric oxide synthase (eNOS) function may be developed as a potential contributor to the pathogenesis of vascular injury. In this study, we investigated early alterations of eNOS signaling in human umbilical venous endothelial cells (HUVECs) exposed to X-ray radiation. We found that ionizing radiation increased eNOS phosphorylation at Ser-1177 and dephosphorylation at Thr-495 in HUVECs in a dose-dependent (≤. 20. Gy) and time-dependent (6-72. h) manner. The total expression levels of eNOS were unchanged by radiation. Although a transient but significant increase in extracellular signal-regulated protein kinase 1/2 (ERK1/2) phosphorylation and a biphasic decline in Akt phosphorylation were observed after irradiation, these inhibitors were without effect on the radiation-induced changes in eNOS phosphorylation. There was an increase in protein kinase C-βII (PKC-βII) expression and the ablation of PKC-βII by small interfering RNA (siRNA) negated the radiation effect on the two eNOS phosphorylation events. Furthermore, when the radiation-induced increase in reactive oxygen species (ROS) generation was prevented by the anti-oxidant N-acetyl-. l-cysteine, eNOS Ser-1177 phosphorylation and Thr-495 dephosphorylation in irradiated HUVECs were significantly reduced. However, transfection of PKC-β siRNA did not alter ROS production after irradiation, and NAC failed to block the radiation-induced increase in PKC-βII expression. Taken together, our results suggest that ionizing radiation-induced eNOS activation in human vascular endothelial cells is attributed to both the up-regulation of PKC-βII and the increase in ROS generation which were independent of each other.

本文言語English
ページ(範囲)55-65
ページ数11
ジャーナルVascular Pharmacology
70
DOI
出版ステータスPublished - 2015 7 1

ASJC Scopus subject areas

  • Physiology
  • Molecular Medicine
  • Pharmacology

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