کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6097081 | 1209900 | 2007 | 18 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
The Lysophosphatidic Acid Type 2 Receptor Is Required for Protection Against Radiation-Induced Intestinal Injury
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کلمات کلیدی
PI3KTNFEDGLPATLCLPPCHXERKPTXBSA - BSAOtp - OTPbovine serum albumin - آلبومین سرم گاوlysophosphatidic acid - اسید لیسفسفیدیدBrdU - بروموداکسی اوریدینbromodeoxyuridine - برومودسوویریدینpertussis toxin - سموم سورافنیcycloheximide - سیکلوهایسیمیدtumor necrosis factor - فاکتور نکروز تومورphosphoinositide 3-kinase - فسفینوزیتید 3-کینازLipid phosphate phosphatase - لیپید فسفات فسفاتازMEK - مجاهدین خلقknockout - ناکاوتEndothelial differentiation gene - ژن تمایز اندوتلیالthin-layer chromatography - کروماتوگرافی نازک لایهExtracellular signal–regulated kinase - کیناز تنظیم شده با سیگنال غیر سلولی
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
بیماریهای گوارشی
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چکیده انگلیسی
Background & Aims: We recently identified lysophosphatidic acid (LPA) as a potent antiapoptotic agent for the intestinal epithelium. The objective of the present study was to evaluate the effect of octadecenyl thiophosphate (OTP), a novel rationally designed, metabolically stabilized LPA mimic, on radiation-induced apoptosis of intestinal epithelial cells in vitro and in vivo. Methods: The receptors and signaling pathways activated by OTP were examined in IEC-6 and RH7777 cell lines and wild-type and LPA1 and LPA2 knockout mice exposed to different apoptotic stimuli. Results: OTP was more efficacious than LPA in reducing gamma irradiation-, camptothecin-, or tumor necrosis factor α/cycloheximide-induced apoptosis and caspase-3-8, and caspase-9 activity in the IEC-6 cell line. In RH7777 cells lacking LPA receptors, OTP selectively protected LPA2 but not LPA1 and LPA3 transfectants. In C57BL/6 and LPA1 knockout mice exposed to 15 Gy gamma irradiation, orally applied OTP reduced the number of apoptotic bodies and activated caspase-3-positive cells but was ineffective in LPA2 knockout mice. OTP, with higher efficacy than LPA, enhanced intestinal crypt survival in C57BL/6 mice but was without any effect in LPA2 knockout mice. Intraperitoneally administered OTP reduced death caused by lethal dose (LD)100/30 radiation by 50%. Conclusions: Our data indicate that OTP is a highly effective antiapoptotic agent that engages similar prosurvival pathways to LPA through the LPA2 receptor subtype.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Gastroenterology - Volume 132, Issue 5, May 2007, Pages 1834-1851
Journal: Gastroenterology - Volume 132, Issue 5, May 2007, Pages 1834-1851
نویسندگان
Wenlin Deng, Shuyu E, Ryoko Tsukahara, William J. Valentine, Gangadhar Durgam, Veeresa Gududuru, Louisa Balazs, Venkatraman Manickam, Marcello Arsura, Lester Vanmiddlesworth, Leonard R. Johnson, Abby L. Parrill, Duane D. Miller, Gabor Tigyi,