کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1983621 | 1539908 | 2013 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Knockdown of FAM3B triggers cell apoptosis through p53-dependent pathway
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کلمات کلیدی
p53PARPFADDnecrostatin-1FAM3B3-(4,5-cimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide - 3- (4،5-سمتیلیتیازول-2-ییل) -2،5-دی فینیل تترازولیم برومیدMdm2 - MDM2MTT - MTTNec-1 - NEC-1RNA interference - RNA تداخل کنندهRNAi - RNA سرکوبگر،RNA مداخلهگر، RNA خاموش کنندهBax - باکسFas-associated death domain - حوزه مرگ مرتبط FasApoptosis - خزان یاختهایCell viability - زنده ماندن سلولlactate dehydrogenase - لاکتات دهیدروژناز LDH - لاکتات دهیدروژناز به صورت مختصر شده LDH PANDER - پاندرBcl-2-associated X protein - پروتئین X مرتبط با Bcl-2Propidium iodide - پروتئین یدیدBAK - پشتpoly (ADP-ribose) polymerase-1 - پلی (ADP-ribose) پلیمراز-1caspase - کسپاز یا کاسپاز
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
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چکیده انگلیسی
FAM3B, also named PANDER, is a cytokine-like protein identified in 2002. Previous studies showed that FAM3B regulates glucose and lipid metabolism through interaction with liver and endocrine pancreas. FAM3B is also expressed by other tissues but its basic function is unclear. In this study, we found that FAM3B was expressed in mouse colon, intestine, liver and lung tissues and multiple types of cell lines, including murine pancreatic β-cell (Min6), microglia (N9) and muscle cell (C2C12); human colon cancer cells (HCT8, HCT116, HT29), hepatocyte (HL-7702), hepatocellular carcinoma cell (SMMC-7721) and lung carcinoma cell (A549). Inhibition of FAM3B expression by RNA interference induced apoptotic cell death of HCT8, HCT116, A549, N9, C2C12 and Min6 cells and decreased cell viability of HL-7702 and murine primary hepatocytes. Further studies with HCT8 cells showed that knockdown of FAM3B increased the protein levels of membrane-bound Fas and Bax, reduced the expression of Bcl-2, promoted the cleavage of caspases-8, -3, -9 and PARP, and the nuclear translocation of cleaved PARP. These results suggest that FAM3B silencing activates both extrinsic and intrinsic apoptotic pathways. Mechanistic studies showed that neutralizing antibody against Fas or silencing Fas-associated death domain had no effect on, while caspase inhibitors could significantly reverse FAM3B knockdown induced apoptosis, suggesting Fas and death receptor mediated extrinsic apoptotic pathway is not involved in FAM3B silencing induced apoptosis. Further studies showed that p53 was significantly upregulated after FAM3B knockdown. Silencing p53 could almost completely reverse FAM3B knockdown induced upregulation of Bax, downregulation of Bcl-2, cleavage of caspases-8, -9, -3, and apoptotic cell death, suggesting p53-dependent pathway plays critical roles in FAM3B silencing induced apoptosis. Studies with HCT116 cells confirmed that inhibition of FAM3B expression induced apoptosis through p53-dependent pathway. Furthermore, knockdown of FAM3B reduced the protein level of Mdm2 and promoted p53 phosphorylation. Taken together, our studies demonstrated that silencing FAM3B promoted p53 phosphorylation and induced p53 accumulation by decreasing Mdm2 expression, which resulted in apoptotic cell death.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: The International Journal of Biochemistry & Cell Biology - Volume 45, Issue 3, March 2013, Pages 684-691
Journal: The International Journal of Biochemistry & Cell Biology - Volume 45, Issue 3, March 2013, Pages 684-691
نویسندگان
Haiwei Mou, Zongmeng Li, Pengle Yao, Shu Zhuo, Wei Luan, Bo Deng, Lihua Qian, Mengmei Yang, Hong Mei, Yingying Le,