Cardiolipin loss induced by cPLA2-mediated mitochondrial dysfunction and neuronal death after spinal

• 作 者: Nai-kui Liu Ling-xiao Deng Miao Wang Qing-bo Lu Xiang-bin Wu Chunyan Wang Xianling Han Jin-lian Li Si-wei You Xiao-Ming Xu
• 机 构: Spinal Cord and Brain Injury Group, Stark Neurosciences Research Institute, and Department of Neurol
• 出 处: Joint Symposium of 2016 International Neural Regeneration Sy
• 发表日期: 2016年8期
• 关键词: spinal cord injury cardiolipin cytosolic phospholipiase A2 neuronal death

　　Traumatic spinal cord injury (SCI) is prevalent in the United States,with more than 11,000 cases every year (https://www.nscisc.uab.edu) (2012).To date,there is no effective pharmacological treatment for SCI (Rabchevsky et al.,2011).A deep understanding of the molecular mechanisms underlying functional deficits in patients with SCI is crucial for developing novel strategies for treating it.Phospholipids are the main components of the neural cell membrane.Although alteration of phospholipids has long been associated with SCI,its specific role in mediating damage and signaling cascades is still not well understood (Hall and Braughler,1986;Braughler and Hall,1992;Liu and Xu,2010).Recently,a novel lipid signaling pathway,i.e.,the cardiolipin (CL) signaling pathway,controlling cell death/apoptosis has emerged.CL is a structurally unique dimeric phospholipid that is exclusively expressed on the inner mitochondrial membrane where it is required for optimal mitochon-drial function (Chicco and Sparagna,2007).In addition to its role in maintaining membrane potential and architecture,CL is known to provide essential structural and functional support to several proteins involved in mitochondrial bioenergetics (Chicco and Sparagna,2007).Recently,CL has been shown to be an important player in the control of the mitochondrial phase of apoptosis (Kagan et al.,2005;Chicco and Sparagna,2007).The importance of CL in mitochondrial function sug-gests that any disturbance of the CL profile may result in mitochondrial dysfunction leading to cell death.Alteration (loss and peroxidation) of CL has been associated with mitochondrial dysfunction and cell death in multiple tissues in a variety of pathological conditions including ischemia,hypothyroidism,aging,heart failure,and traumatic brain injury (Bayir et al.,2007;Chicco and Sparagna,2007).