대한신장학회

논문분류	춘계학술대회 초록집
제목	Cilastatin preconditioning attenuates oxidative stress and apoptosis through hypoxia inducible factor-1α activation in renal ischemia-reperfusion injury
저자	Yu Ah Hong1, So Young Jung2, Keum Jin Yang2, Jung Ho Kim1, Yoon Kyung Chang1, Cheol Whee Park3, Chul Woo Yang3, Suk Young Kim1, Dai Sig Im4, Hyeon Seok Hwang5
출판정보	2018; 2018(1):
키워드	cilastatin \| HIF-1a \| kidney IR injury \| oxidative stress \| apoptosis
초록	Objectives: Cilastatin is a specific inhibitor of renal dehydrodipeptidase-1 (DHP-1). We investigated whether cilastatin preconditioning attenuates apoptosis via hypoxia inducible factor-1α (HIF-1α) activation in renal ischemia-reperfusion (IR) injury. Methods: In vitro, human proximal tubular cell line (HK-2) was exposed to ischemia by mineral oil monolayer. In vivo, Male C57BL/6 mice were subjected to 23 min of bilateral kidney ischemia and 24 h reperfusion. The effects of cilastatin preconditioning were investigated in IR injury models. Results: In HK-2 cells, HIF-1α expression was most highly increased at 200 μg/ml and 6 h after cilastatin preconditioning. Cilastatin increased HIF-1α translation via phosphorylation of Akt and mTOR expression followed by increases of EPO and VEGF expression in a time-dependent manner. Cilastatin did not affect the expression of HPD and pVHL expression, but the ubiquitination of HIF-1α expression was significantly decreased after cilastatin preconditioning. Cilastatin prevented the HK-2 cell death induced by IR injury. This protective effect of cilastatin in IR-exposed cells was offset by YC-1 or HIF-1α small interfering RNA. In consistent with in vitro study, HIF-1α expression and its upstream and downstream signaling were significantly increased by cilastatin in a time dependent manner. Cilastatin preconditioning further increased HIF-1α expression and decreased HIF-1α ubiquitination in mice kidney with IR injury. Cilastatin decreased serum creatinine level and tubular necrosis were decreased in mice kidney with IR injury. Cilastatin decreased tissue MDA levels, expression of Bax/Bcl-2 and TUNEL-positive cells in mice kidney with IR injury. Conclusions: Cilastatin preconditioning attenuates oxidative stress and apoptosis through HIF-1α activation induced by activating Akt-mTOR signaling and inhibiting ubiquitination of HIF-1α in renal IR injury.
원문(PDF)	PDF 원문보기

간행물 검색

대한신장학회 회원관리 규정