کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10904056 | 1086554 | 2014 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Molecular mechanism of 2-APB-induced Ca2+ influx in external acidification in PC12
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کلمات کلیدی
transient receptor potential melastatin 7store-operated Ca2+STIMTRISTRPM7ECDRT-PCRPC122-aminoethoxydiphenyl borate2-APBIP3RNMDGTRPVDMSO - DMSOPCA - PCASmall interfering RNA - RNA تداخل کوچکsiRNA - siRNA[Ca2+]i - [Ca2 +] iPerchloric acid - اسید پرکلریکDopamine secretion - ترشح دوپامینTris(hydroxymethyl)aminomethane - تریس (هیدروکسی متیل) آمینومتانElectrochemical detection - تشخیص الکتروشیمیاییDopamine - دوپامینDimethyl sulfoxide - دیمتیل سولفواکسیدSOC - سیستم روی یک تراشهendoplasmic reticulum - شبکه آندوپلاسمی intracellular calcium concentration - غلظت کلسیم داخل سلولیreverse transcription-polymerase chain reaction - واکنش زنجیره ای رونویسی-پلیمراز معکوسtransient receptor potential vanilloid - پتانسیل ترانزیتی وینیلوئیدProton - پروتون
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
2-Aminoethoxydiphenyl borate (2-APB) is used as a pharmacological tool because it antagonizes inositol 1,4,5-trisphosphate receptors and store-operated Ca2+ (SOC) channels, and activates some TRP channels. Recently, we reported that 2-APB enhanced the increase in cytotoxic [Ca2+]i, resulting in cell death under external acidic conditions in rat pheochromocytoma cell line PC12. However, the molecular mechanism and functional role of the 2-APB-induced Ca2+ influx in PC12 have not been clarified. In this study, to identify the possible target for the action of 2-APB we examined the pharmacological and molecular properties of [Ca2+]i and secretory responses to 2-APB under extracellular low pH conditions. 2-APB dose-dependently induced a [Ca2+]i increase and dopamine release, which were greatly enhanced by the external acidification (pH 6.5). [Ca2+]i and secretory responses to 2-APB at pH 6.5 were inhibited by the removal of extracellular Ca2+ and SOC channel blockers such as SK&F96365, La3+ and Gd3+. PC12 expressed all SOC channel molecules, Orai 1, Orai 2 and Orai 3. When we used an siRNA system, downregulation of Orai 3, but not Orai 1 and Orai 2, attenuated both [Ca2+]i and secretory responses to 2-APB. These results suggest that 2-APB evokes external acid-dependent increases of [Ca2+]i and dopamine release in PC12 through the activation of Orai 3. The present results indicate that 2-APB may be a useful pharmacological tool for Orai channel-related signaling.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Cell Research - Volume 323, Issue 2, 1 May 2014, Pages 337-345
Journal: Experimental Cell Research - Volume 323, Issue 2, 1 May 2014, Pages 337-345
نویسندگان
Kenji Takahashi, Minae Yokota, Toshio Ohta,