کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
4342635 | 1295881 | 2007 | 16 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Effect of tricyclodecan-9-yl potassium xanthate (D609) on phospholipid metabolism and cell death during oxygen-glucose deprivation in PC12 cells
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کلمات کلیدی
rat pheochromocytoma cellN-SmaseA-SMasePC-PLCCa2+-independent phospholipase A2iPLA2D609sPLA2PLA2SMasePARPTBSTPLDcPLA2OGDCCTCPTHRPphosphatidylcholine-phospholipase CTLCFFANAC1,2-Diacylglycerol - 1،2-دیسیل گلیسرولN-acetylcysteine - N-استیل سیستئین[Ca2+]i - [Ca2 +] iphospholipase A2 - آنزیم فسفولیپاز A2 acidic sphingomyelinase - اسفنجومیلیناز اسیدیsphingomyelin - اسفنگومیلینsphingomyelinase - اسپینگومایینازSecretory phospholipase A2 - اسید فسفولیپاز A2Free fatty acids - اسیدهای چرب آِزادIntracellular Ca2+ - داخل سلولی Ca2 +DAG - روزceramide - سرامیدPC12 cell - سلول PC12phycoerythrin - فایکوئیریدینphosphatidylcholine - فسفاتیدیل کولینPhosphatidylserine - فسفاتیدیلسرینcytosolic phospholipase A2 - فسفولیپاز A2 سیتوزولPhospholipase D - فسفولیپاز DPhospholipases - فسفولیپازهاlactate dehydrogenase - لاکتات دهیدروژناز LDH - لاکتات دهیدروژناز به صورت مختصر شده LDH Oxygen-glucose deprivation - محرومیت گلوکز اکسیژنHorseradish peroxidase - پراکسیداز هوررادیشPropidium iodide - پروتئین یدیدpoly-ADP ribose polymerase - پلی-ADP ریبوز پلی مرازthin layer chromatography - کروماتوگرافی لایه نازک
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب (عمومی)
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چکیده انگلیسی
Alterations in lipid metabolism play an integral role in neuronal death in cerebral ischemia. Here we used an in vitro model, oxygen-glucose deprivation (OGD) of rat pheochromocytoma (PC12) cells, and analyzed changes in phosphatidylcholine (PC) and sphingomyelin (SM) metabolism. OGD (4-8 h) of PC12 cells triggered a dramatic reduction in PC and SM levels, and a significant increase in ceramide. OGD also caused increases in phosphatidylcholine-phospholipase C (PC-PLC) and phospholipase D (PLD) activities and PLD2 protein expression, and reduction in cytidine triphosphate:phosphocholine cytidylyltransferase-α (CCTα, the rate-limiting enzyme in PC synthesis) protein expression and activity. Phospholipase A2 activity and expression were unaltered during OGD. Increased neutral sphingomyelinase activity during OGD could account for SM loss and increased ceramide. Surprisingly, treatment with PC-PLC inhibitor tricyclodecan-9-yl potassium xanthate (D609) aggravated cell death in PC12 cells during OGD. D609 was cytotoxic only during OGD; cell death could be prevented by inclusion of sera, glucose or oxygen. During OGD, D609 caused further loss of PC and SM, depletion of 1,2-diacylglycerol (DAG), increase in ceramide and free fatty acids (FFA), cytochrome c release from mitochondria, increases in intracellular Ca2+ ([Ca2+]i), poly-ADP ribose polymerase (PARP) cleavage and phosphatidylserine externalization, indicative of apoptotic cell death. Exogenous PC during OGD in PC12 cells with D609 attenuated PC, SM loss, restored DAG, attenuated ceramide levels, decreased cytochrome c release, PARP cleavage, annexin V binding, attenuated the increase in [Ca2+]i, FFA release, and significantly increased cell viability. Exogenous PC may have elicited these effects by restoring membrane PC levels. A tentative scheme depicting the mechanism of action of D609 (inhibiting PC-PLC, SM synthase, PC synthesis at the CDP-choline-1,2-diacylglycerol phosphocholine transferase (CPT) step and causing mitochondrial dysfunction) has been proposed based on our observations and literature.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience - Volume 146, Issue 3, 25 May 2007, Pages 946-961
Journal: Neuroscience - Volume 146, Issue 3, 25 May 2007, Pages 946-961
نویسندگان
E.C. Larsen, J.F. Hatcher, R.M. Adibhatla,