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Involvement of the miR-137-3pCAPN-2 Interaction in Ischemia-Reperfusion-Induced Neuronal Apoptosis through Modulation of p35 Cleavage and Subsequent Caspase-8 Overactivation
المؤلفون المشاركون
Wang, He
Yu, Qian
Zhang, Zai-Li
Ma, Hong
Li, Xiao-Qian
المصدر
Oxidative Medicine and Cellular Longevity
العدد
المجلد 2020، العدد 2020 (31 ديسمبر/كانون الأول 2020)، ص ص. 1-17، 17ص.
الناشر
Hindawi Publishing Corporation
تاريخ النشر
2020-12-10
دولة النشر
مصر
عدد الصفحات
17
التخصصات الرئيسية
الملخص EN
Background.
Neuron survival after ischemia-reperfusion (IR) injury is the primary determinant of motor function prognosis.
MicroRNA- (miR-) based gene therapy has gained attention recently.
Our previous work explored the mechanisms by which miR-137-3p modulates neuronal apoptosis in both in vivo and in vitro IR models.
Methods.
IR-induced motor dysfunction and spinal calpain (CAPN) subtype expression and subcellular localization were detected within 12 h post IR.
Dysregulated miRs, including miR-137-3p, were identified by miR microarray analysis and confirmed by PCR.
A luciferase assay confirmed CAPN-2 as a corresponding target of miR-137-3p, and their modulation of motor function was evaluated by intrathecal injection with synthetic miRs.
CAPN-2 activity was measured by the intracellular Ca2+ concentration and mean fluorescence intensity in vitro.
Neuronal apoptosis was detected by flow cytometry and TUNEL assay.
The activities of p35, p25, Cdk5, and caspase-8 were evaluated by ELISA and Western blot after transfection with specific inhibitors and miRs.
Results.
The IR-induced motor dysfunction time course was closely associated with upregulated expression of the CAPN-2 protein, which was mainly localized in neurons.
The miR-137-3p/CAPN-2 interaction was confirmed by luciferase assay.
The miR-137-3p mimic significantly improved IR-induced motor dysfunction and decreased CAPN-2 expression, even in combination with recombinant rat calpain-2 (rr-CALP2) injection, whereas the miR-137-3p inhibitor reversed these effects.
Similar changes in the intracellular Ca2+ concentration, CAPN-2 expression, and CAPN-2 activity were observed when cells were exposed to oxygen-glucose deprivation and reperfusion (OGD/R) and transfected with synthetic miRs in vitro.
Moreover, double fluorescence revealed identical neuronal localization of CAPN-2, p35, p25, and caspase-8.
The decrease in CAPN-2 expression and activity was accompanied by the opposite changes in p35 activity and protein expression in cells transfected with the miR-137-3p mimic, roscovitine (a Cdk5 inhibitor), or Z-IETD-FMK (a caspase-8 inhibitor).
Correspondingly, the abovementioned treatments resulted in a higher neuron survival rate than that of untreated neurons, as indicated by decreases in the apoptotic cell percentage and p25, Cdk5, caspase-8, and caspase-3 protein expression.
Conclusions.
The miR-137-3p/CAPN-2 interaction modulates neuronal apoptosis during IR injury, possibly by inhibiting CAPN-2, which leads to p35 cleavage and inhibition of subsequent p25/Cdk5 and caspase-8 overactivation.
نمط استشهاد جمعية علماء النفس الأمريكية (APA)
Wang, He& Yu, Qian& Zhang, Zai-Li& Ma, Hong& Li, Xiao-Qian. 2020. Involvement of the miR-137-3pCAPN-2 Interaction in Ischemia-Reperfusion-Induced Neuronal Apoptosis through Modulation of p35 Cleavage and Subsequent Caspase-8 Overactivation. Oxidative Medicine and Cellular Longevity،Vol. 2020, no. 2020, pp.1-17.
https://search.emarefa.net/detail/BIM-1204008
نمط استشهاد الجمعية الأمريكية للغات الحديثة (MLA)
Wang, He…[et al.]. Involvement of the miR-137-3pCAPN-2 Interaction in Ischemia-Reperfusion-Induced Neuronal Apoptosis through Modulation of p35 Cleavage and Subsequent Caspase-8 Overactivation. Oxidative Medicine and Cellular Longevity No. 2020 (2020), pp.1-17.
https://search.emarefa.net/detail/BIM-1204008
نمط استشهاد الجمعية الطبية الأمريكية (AMA)
Wang, He& Yu, Qian& Zhang, Zai-Li& Ma, Hong& Li, Xiao-Qian. Involvement of the miR-137-3pCAPN-2 Interaction in Ischemia-Reperfusion-Induced Neuronal Apoptosis through Modulation of p35 Cleavage and Subsequent Caspase-8 Overactivation. Oxidative Medicine and Cellular Longevity. 2020. Vol. 2020, no. 2020, pp.1-17.
https://search.emarefa.net/detail/BIM-1204008
نوع البيانات
مقالات
لغة النص
الإنجليزية
الملاحظات
Includes bibliographical references
رقم السجل
BIM-1204008
قاعدة معامل التأثير والاستشهادات المرجعية العربي "ارسيف Arcif"
أضخم قاعدة بيانات عربية للاستشهادات المرجعية للمجلات العلمية المحكمة الصادرة في العالم العربي
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