کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10738087 | 1046682 | 2011 | 13 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
ROS-activated p38 MAPK/ERK-Akt cascade plays a central role in palmitic acid-stimulated hepatocyte proliferation
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کلمات کلیدی
NACnuclear factor erythroid 2 p45-related factor 2PCNA3NPFFAsc-Jun NH2-terminal kinaseERKOXPHOSNrf2CATJnk2′,7′-dichlorofluorescin diacetate - 2 '، 7'-dichlorofluorescin diacetateCDKs - CDK هاH2DCFDA - H2DCFD بهMAPKs - MAPK هاN-acetylcysteine - N-استیل سیستئینROS - ROSProliferating Cell Nuclear Antigen - آنتیژن هسته ای تکثیر سلولیAkt - آکتfatty acid synthase - اسید چرب سنتازFree fatty acids - اسیدهای چرب آِزادProliferation - ترویجretinoblastoma - رتینوبلاستوما، تومور شبکیهendoplasmic reticulum - شبکه آندوپلاسمی Fasn - فسادOxidative phosphorylation - فسفوریلاسیون اکسیداتیوPalmitic acid - پالمیتیک اسیدprotein kinase B - پروتئین کیناز BCell cycle - چرخه سلولیCatalase - کاتالازextracellular signal-regulated kinase - کیناز تنظیم شده سیگنال خارج سلولیcyclin-dependent kinases - کیناز وابسته به سیکلینmitogen-activated protein kinases - کیناز پروتئین فعال MitogenReactive oxygen species - گونههای فعال اکسیژن
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
In the past years, free fatty acids (FFAs) and obesity have been reported to play an important role in cancer development. Palmitic acid (PA) is the most prevalent saturated FFA in circulation. However, the mechanism underlying the effect of PA on cell proliferation is still to be elucidated. In this report, we, for the first time, investigate the signaling pathway in human normal hepatocytes (QZG) responsible for PA-induced proliferation. The results demonstrate that PA promotes cell cycle progression, accelerates cell proliferation, and induces a transient and sequential activation of a series of kinases. The employment of several inhibitors and antioxidants indicates that a ROS-induced stress-sensitive p38 MAPK/ERK-Akt cascade plays a critical role in the regulation of PA on cell cycle and cell proliferation. Moreover, PA dose and time dependently activates Nrf2 and this activation relies on ROS-induced stimulation of p38 MAPK/ERK-Akt signaling, demonstrating that Nrf2 activation may be associated with the regulation of PA on cell cycle transition and proliferation. In conclusion, our study elucidates the importance of PA metabolism on cell proliferation, and suggests that PA stimulates hepatocyte proliferation through activating the ROS-p38 MAPK/ERK-Akt cascade which is intersected with the activation of Nrf2 and that the effect of ROS on signal transduction is in a dose- and time-dependent manner. All the above noted provide a new clue for the central role of ROS in cell proliferation and tumorigenesis.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Free Radical Biology and Medicine - Volume 51, Issue 2, 15 July 2011, Pages 539-551
Journal: Free Radical Biology and Medicine - Volume 51, Issue 2, 15 July 2011, Pages 539-551
نویسندگان
Xin Wang, Jiang Z. Liu, Jun X. Hu, Hao Wu, Yu L. Li, Hong L. Chen, Hua Bai, Chun X. Hai,