Expression of MICU1 after experimental focal cerebral ischemia in adult rats

Liang Wang,Wang Wang,Kun Zhang,Tong Zhang,Xinying Tian,Xiaoyun Liu,Bin Li,Jiajia Yan,Li Guo

doi:10.1186/s41016-017-0078-3

Abstract

BackgroundMitochondrial Ca2+ uptake is a pivotal pathophysiological process for neuronal survival when subjected to ischemic insult. Mitochondrial calcium uptake 1 (MICU1) has been demonstrated as a key regulator of the mitochondrial calcium uniporter (MCU), identified as a tetrameric highly specific channel that modulates mitochondrial Ca2+ uptake.MethodsAdult male Sprague–Dawley (SD) rats underwent middle cerebral artery occlusion (MCAO) to create the standard focal cerebral ischemia model. The permanent MCAO approach utilized the intraluminal approach. Neurological examination, and subsequent histological characterization of cerebral infarcts using triphenyltetrazolium chloride staining, as well as Western blot, immunohistochemical staining, and real-time quantitative polymerase chain reaction assays were employed to assess the functional effects of MICU1 and its expression in the brain.ResultsAnimals exposed to MCAO displayed the typical neurological deficit accompanied by cortical and subcortical infarction at 72 h post-stroke. The expression of MICU1, with co-localization with neurons, was detected at different time points (6 h and 12 h) after ischemic damage. Altogether, these observations revealed an up-regulation of MICU1 expression in the early stages of cerebral ischemia.ConclusionThe results demonstrated that MICU1 was upregulated in neurons at the acute phase of ischemic stroke. Because MICU1 has been previously shown to participate in mitochondrial Ca2+ uptake mediated by MCU, our study further implicates the involvement of MICU1 in calcium overload-induced cell death which is closely associated with stroke.

Highlights

Mitochondrial Ca2+ uptake is a pivotal pathophysiological process for neuronal survival when subjected to ischemic insult
Mitochondrial calcium uptake 1 (MICU1) expression is significantly increased at protein level after cerebral ischemia We detected the expression of MICU1 at protein level by western blot with whole tissue lysates collected from the rats’ brain regions from bregma 1 to −1 mm
Our results suggested that the expression of MICU1 was and 12 h after ischemia

Summary

Introduction

Mitochondrial Ca2+ uptake is a pivotal pathophysiological process for neuronal survival when subjected to ischemic insult. Mitochondrial calcium uptake 1 (MICU1) has been demonstrated as a key regulator of the mitochondrial calcium uniporter (MCU), identified as a tetrameric highly specific channel that modulates mitochondrial Ca2+ uptake. A widely postulated cell death pathway implicated in stroke involves mitochondrial Ca2+ overload induced by mitochondrial Ca2+ uptake. Such aberrant mitochondrial Ca2+ overload has been shown to play a vital role in the onset and progression of pathophysiological process in the early phases of ischemia [1]. Previous studies have (MCU), which possesses two transmembrane domains and forms tetrameric highly specific mitochondrial Ca2+ channels, is responsible for the mitochondrial Ca2+ uptake [2]. Mitochondrial Ca2+ uptake 1 (MICU1) has been demonstrated to be a key regulator of MCU [3]

Methods

Results

Conclusion