Kaempferol Suppresses Cisplatin-Induced Apoptosis Via Inductions of Heme Oxygenase-1 and Glutamate-Cysteine Ligase Catalytic Subunit in HEI-OC1 cells

被引：51

作者：

Gao, Shang Shang ^{[1
,2
]}

Choi, Byung-Min ^{[1
,2
]}

Chen, Xiao Yan ^{[1
,2
]}

Zhu, Ri Zhe ^{[1
,2
]}

Kim, Youngho ^{[1
,2
]}

So, HongSeob ^{[1
,3
]}

Park, Raekil ^{[1
,3
]}

Sung, Meesook ^{[4
]}

Kim, Bok-Ryang ^{[1
,2
]}

机构：

[1] Wonkwang Univ, Vestibulocochlear Res Ctr, Sch Med, Chonbuk 570749, South Korea

[2] Wonkwang Univ, Dept Biochem, Sch Med, Chonbuk 570749, South Korea

[3] Wonkwang Univ, Dept Microbiol, Sch Med, Chonbuk 570749, South Korea

[4] Kwandong Univ, Dept Biochem, Coll Med, Kangnung 210701, South Korea

来源：

PHARMACEUTICAL RESEARCH | 2010年 / 27卷 / 02期

关键词：

cisplatin; kaempferol; MAPK; Nrf2; (HO-1; GCLC); oxidative stress; MEDIATED GENE-EXPRESSION; OXIDATIVE STRESS; AUDITORY CELLS; TRANSCRIPTIONAL REGULATION; SIGNALING PATHWAY; DOWN-REGULATION; ANTIOXIDANT; ACTIVATION; NRF2; GLUTATHIONE;

D O I：

10.1007/s11095-009-0003-3

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

The present study was undertaken to elucidate the chemoprotective mechanism of kaempferol, which possesses anti-oxidative and anti-apoptotic properties. House Ear Institute-Organ of Corti 1 (HEI-OC1) cells were treated with kaempferol in the presence or absence of cisplatin. Cisplatin-induced oxidative stress was assessed by analysis of Comet assay, DNA-laddering assay and activation of caspases. Heme oxygenase-1 (HO-1), mitogen-activated protein kinase (MAPK) pathway and nuclear factor-E2-related factor 2 (Nrf2) were measured by Western blot analysis. Transfection of small interfering RNAs (siRNA), glutathione (GSH) assay and RT-PCR were performed in this study. Kaempferol protected cells against cisplatin-induced apoptosis in a dose-dependent manner in HEI-OC1 cells. Kaempferol-induced HO-1 expression protected against cell death though the c-Jun N-terminal kinase (JNK) pathway and by the aid of Nrf2 translocation. Kaempferol increased the cellular level of GSH and the expression of GCLC time-dependently. siRNA GCLC blocked the increase of GSH level by kaempferol and the protective effect of kaempferol against cisplatin-induced cell death. The expression of HO-1 by kaempferol inhibits cisplatin-induced apoptosis in HEI-OC1 cells, and the mechanism of protective effect is also associated with its inductive effect of GCLC expression.

引用

页码：235 / 245

页数：11

共 48 条

[1] The antioxidant role of a reagent, 2′,7′-dichlorodihydrofluorescin diacetate, detecting reactive-oxygen species and blocking the induction of heme oxygenase-1 and preventing cytotoxicity [J].