کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2012060 1067023 2011 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Anti-apoptotic effect of phloretin on cisplatin-induced apoptosis in HEI-OC1 auditory cells
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Anti-apoptotic effect of phloretin on cisplatin-induced apoptosis in HEI-OC1 auditory cells
چکیده انگلیسی

Cisplatin is a highly effective chemotherapeutic agent, but it has significant ototoxic side effects. Apoptosis is an important mechanism of cochlear hair cell loss following exposure to cisplatin. The present study examined the effects of phloretin, a natural polyphenolic compound found in apples and pears, on cisplatin-induced apoptosis. We found that phloretin induced the expression of heme oxygenase-1 (HO-1) protein in a concentration- and time-dependent manner. Phloretin induced nuclear factor-E2-related factor 2 (Nrf2) nuclear translocation, and dominant-negative Nrf2 attenuated phloretin-induced expression of HO-1. Phloretin activated the JNK, ERK and p38 mitogen-activated protein kinase (MAPK) pathways, and the JNK pathway played an important role in phloretin-induced HO-1 expression. Phloretin protected the cells against cisplatin-induced apoptosis. The protective effect of phloretin was abrogated by zinc protoporphyrin IX (ZnPP IX), a HO inhibitor. Furthermore, phloretin pretreatment inhibited mitochondrial dysfunction and the activation of caspases. These results demonstrate that the expression of HO-1 induced by phloretin is mediated by both the JNK pathway and Nrf2; the expression inhibits cisplatin-induced apoptosis in HEI-OC1 cells.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Pharmacological Reports - Volume 63, Issue 3, May–June 2011, Pages 708–716
نویسندگان
, , , , ,