Contradictory Effects of Superoxide and Hydrogen Peroxide on KCa3.1 in Human Endothelial Cells

• 영문명: Contradictory Effects of Superoxide and Hydrogen Peroxide on K_Ca3.1 in Human Endothelial Cells
• 발행기관: 대한생리학회-대한약리학회
• 저자명: Shinkyu Choi Hye-Young Na Ji Aee Kim Sung-Eun Cho Suk Hyo Suh
• 간행물 정보: 『The Korean Journal of Physiology & Pharmacology』제17권 제3호, 181~187쪽, 전체 7쪽
• 주제분류: 의약학 > 의학일반
• 파일형태: PDF
• 발행일자: 2013.01.01

영문 초록

Reactive oxygen species (ROS) are generated in various cells, including vascular smooth muscle and endothelial cells, and regulate ion channel functions. K_Ca3.1 plays an important role in endothelial functions. However, the effects of superoxide and hydrogen peroxide radicals on the expression of this ion channel in the endothelium remain unclear. In this study, we examined the effects of ROS donors on K_Ca3.1 expression and the K^＋ current in primary cultured human umbilical vein endothelial cells (HUVECs). The hydrogen peroxide donor, tert-butyl hydroperoxide (TBHP), upregulated K_Ca3.1 expression, while the superoxide donors, xanthine/xanthine oxidase mixture (X/XO) and lysophosphatidylcholine (LPC), downregulated its expression, in a concentration-dependent manner. These ROS donor effects were prevented by antioxidants or superoxide dismustase. Phosphorylated extracellular signal-regulated kinase (pERK) was upregulated by TBHP and downregulated by X/XO. In addition, repressor element-1-silencing transcription factor (REST) was downregulated by TBHP, and upregulated by X/XO. Furthermore, K_Ca3.1 current, which was activated by clamping cells with 1 ՌM Ca^2＋ and applying the K_Ca3.1 activator 1-ethyl-2-benzimidazolinone, was further augmented by TBHP, and inhibited by X/XO. These effects were prevented by antioxidants. The results suggest that hydrogen peroxide increases K_Ca3.1 expression by upregulating pERK and downregulating REST, and augments the K^＋ current. On the other hand, superoxide reduces K_Ca3.1 expression by downregulating pERK and upregulating REST, and inhibits the K^＋ current. ROS thereby play a key role in both physiological and pathological processes in endothelial cells by regulating K_Ca3.1 and endothelial function.

키워드

Ca^2＋-activated K^＋ channel Endothelial cells Hydrogen peroxide Superoxide