Astrocyte-specific glutamate transporter subtype 1 (GLT-1) plays an important role in influencing glutamate excitatory toxicity and preventing the death of excitatory toxic neurons. Although the mammalian target of rapamycin (mTOR)/protein kinase B(Akt)/nuclear factor kappa B signaling cascade is involved in the upregulation of astrocytic GLT-1 in oxygen–glucose deprivation (OGD), it is unclear whether the mTOR/Akt pathway is involved in astrocytic GLT-1 upregulation in OGD and reoxygenation (OGD/R). In this study, we found that the treatment of cultured astrocytes with rapamycin and triciribine led to the decreased astrocytes’ protrusions, smaller nuclei, and an increased apoptotic rate. The inhibitors of mTOR complex 1 significantly increased the expression levels of phosphorylated Akt-Ser473 (p-Akt), phosphorylated Akt-Thr308(p-Akt), and GLT-1, while Akt-specific inhibitors blocked GLT-1 expression, suggesting that the mTOR/Akt pathway is involved in GLT-1 upregulation. We further demonstrated that astrocytes under OGD/R adapted to environmental changes through the mTOR/Akt pathway, mainly by altering cell morphology and apoptosis and upregulating the expression levels of p-Akt and GLT-1. Our results suggested that astrocytes may adapt to short-term ischemic–reperfusion injury by regulating cell morphology, apoptosis and GLT-1 upregulation.
脑卒中是我国国民首位死亡原因,脑梗塞的主要发病机制是血管闭塞或血管栓塞致血流受限,引起脑组织缺血缺氧所致.根据栓子来源不同,有学者提出了TOAST病因学分型,目前针对缺血性卒中不同病因分型的急性期治疗,尤其是心源性栓塞型,国内外指南及专家共识有部分更新,本文以急性缺血性卒中(A IS)病因分型为主线,对近年来国内外更新的A IS指南及专家共识进行解读,以期为临床诊疗方案的选择提供参考,实现个体化最优治疗.
铁自噬(ferritinophagy)是一种调节细胞内铁代谢的选择性自噬,由核受体共激活因子4(NCOA4)介导细胞内铁蛋白转运到自噬溶酶体中降解释放出游离铁,用于多种铁依赖的生理过程.正常生理情况下铁自噬维持着细胞内铁元素的平衡.当铁自噬过度激活时,细胞内过量的铁沉积诱导谷胱甘肽(GS H)耗竭以及谷胱甘肽过氧化物酶4(GPX4)的表达减少,导致细胞膜结构崩溃和破裂,最终引起细胞的铁死亡(ferroptosis).已有研究表明,氧化应激、炎症、兴奋性毒素和凋亡在中枢神经系统损伤的病理生理过程中起着重要作用.近年来,对铁死亡这一以铁依赖性脂质过氧化积累为特征的调节性细胞死亡与中枢神经系统疾病的关系研究越来越多.本文就铁自噬与铁死亡在中枢神经系统疾病中的作用研究进展进行综述.
