MiR-25 Protects Cardiomyocytes against Oxidative Damage by Targeting the Mitochondrial Calcium Uniporter
نویسندگان
چکیده
MicroRNAs (miRNAs) are a class of small non-coding RNAs, whose expression levels vary in different cell types and tissues. Emerging evidence indicates that tissue-specific and -enriched miRNAs are closely associated with cellular development and stress responses in their tissues. MiR-25 has been documented to be abundant in cardiomyocytes, but its function in the heart remains unknown. Here, we report that miR-25 can protect cardiomyocytes against oxidative damage by down-regulating mitochondrial calcium uniporter (MCU). MiR-25 was markedly elevated in response to oxidative stimulation in cardiomyocytes. Further overexpression of miR-25 protected cardiomyocytes against oxidative damage by inactivating the mitochondrial apoptosis pathway. MCU was identified as a potential target of miR-25 by bioinformatical analysis. MCU mRNA level was reversely correlated with miR-25 under the exposure of H2O2, and MCU protein level was largely decreased by miR-25 overexpression. The luciferase reporter assay confirmed that miR-25 bound directly to the 3' untranslated region (UTR) of MCU mRNA. MiR-25 significantly decreased H2O2-induced elevation of mitochondrial Ca2+ concentration, which is likely to be the result of decreased activity of MCU. We conclude that miR-25 targets MCU to protect cardiomyocytes against oxidative damages. This finding provides novel insights into the involvement of miRNAs in oxidative stress in cardiomyocytes.
منابع مشابه
Small Interfering RNA Targeting Mitochondrial Calcium Uniporter Improves Cardiomyocyte Cell Viability in Hypoxia/Reoxygenation Injury by Reducing Calcium Overload
Intracellular Ca2+ mishandling is an underlying mechanism in hypoxia/reoxygenation (H/R) injury that results in mitochondrial dysfunction and cardiomyocytes death. These events are mediated by mitochondrial Ca2+ (mCa2+) overload that is facilitated by the mitochondrial calcium uniporter (MCU) channel. Along this line, we evaluated the effect of siRNA-targeting MCU in cardiomyocytes subjected to...
متن کاملDownregulation of the Mitochondrial Calcium Uniporter by Cancer-Related miR-25
The recently discovered mitochondrial calcium uniporter (MCU) promotes Ca(2+) accumulation into the mitochondrial matrix. We identified in silico miR-25 as a cancer-related MCU-targeting microRNA family and demonstrate that its overexpression in HeLa cells drastically reduces MCU levels and mitochondrial Ca(2+) uptake, while leaving other mitochondrial parameters and cytosolic Ca(2+) signals un...
متن کاملPortulaca oleracea protects H9c2 cardiomyocytes against doxorubicin-induced toxicity via regulation of oxidative stress and apoptosis
Abstract Background and Objectives: Doxorubicin as an effective chemotherapeutic agent is frequently used in various cancers. Nowadays, the application of doxorubicin is limited due to its cardiotoxic effects. The important mechanism which is involved in the cardiac injury of doxorubicin is the generation of reactive oxygen species; therefore antioxidant compounds may reduce cardiotoxicity. ...
متن کاملMicroRNA-145 Protects Cardiomyocytes against Hydrogen Peroxide (H2O2)-Induced Apoptosis through Targeting the Mitochondria Apoptotic Pathway
MicroRNAs, a class of small and non-encoding RNAs that transcriptionally or post-transcriptionally modulate the expression of their target genes, has been implicated as critical regulatory molecules in many cardiovascular diseases, including ischemia/reperfusion induced cardiac injury. Here, we report microRNA-145, a tumor suppressor miRNA, can protect cardiomyocytes from hydrogen peroxide H₂O₂...
متن کاملمروری بر نقش محافظتی ترکیبات پلی فنلی (رسوراترول، کوئرسیتین و کورکومین) بر عملکرد میتوکندری قلب
Mitochondria plays a major role in maintaining homeostasis of heart cells. Mitochondria produce ATP and is the main intracellular source of reactive oxygen species (ROS) which can cause oxidative damage. Free oxygen radicals and oxidative damage are associated with cardiovascular pathology. Antioxidant defense can play an essential role in preventing oxidative damage by controlling free oxygen ...
متن کامل