%0 Journal Article
%T PDGF Suppresses Oxidative Stress Induced Ca2+ Overload and Calpain Activation in Neurons
%A Lian-Shun Zheng
%A Yoko Ishii
%A Qing-Li Zhao
%A Takashi Kondo
%A Masakiyo Sasahara
%J Oxidative Medicine and Cellular Longevity
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/367206
%X Oxidative stress is crucially involved in the pathogenesis of neurological diseases such as stroke and degenerative diseases. We previously demonstrated that platelet-derived growth factors (PDGFs) protected neurons from H2O2-induced oxidative stress and indicated the involvement of PI3K-Akt and MAP kinases as an underlying mechanism. Ca2+ overload has been shown to mediate the neurotoxic effects of oxidative stress and excitotoxicity. We examined the effects of PDGFs on H2O2-induced Ca2+ overload in primary cultured neurons to further clarify their neuroprotective mechanism. H2O2-induced Ca2+ overload in neurons in a dose-dependent manner, while pretreating neurons with PDGF-BB for 24 hours largely suppressed it. In a comparative study, the suppressive effects of PDGF-BB were more potent than those of PDGF-AA. We then evaluated calpain activation, which was induced by Ca2+ overload and mediated both apoptotic and nonapoptotic cell death. H2O2-induced calpain activation in neurons in a dose-dependent manner. Pretreatment of PDGF-BB completely blocked H2O2-induced calpain activation. To the best of our knowledge, the present study is the first to demonstrate the mechanism underlying the neuroprotective effects of PDGF against oxidative stress via the suppression of Ca2+ overload and inactivation of calpain and suggests that PDGF-BB may be a potential therapeutic target of neurological diseases. 1. Introduction Oxidative stress and excitotoxicity play important roles in the pathogenesis of a number of neurological diseases, including ischemic infarction, multiple sclerosis, amyotrophic lateral sclerosis, and Alzheimer¡¯s, Huntington¡¯s, and Parkinson¡¯s diseases [1¨C3]. Ca2+ has been shown to mediate the cytotoxicity of oxidative stress and excitotoxicity, and cellular Ca2+ overload or the perturbation of intracellular Ca2+ compartmentalization induced by these noxious stimuli can cause cytotoxicity and trigger cell death including both apoptotic and necrotic cell death [4¨C6]; however, these mechanisms of cellular injury have yet to be elucidated in adequate detail to prevent and treat neurological diseases [7, 8]. Calpains are calcium-regulated cysteine proteases that have been implicated in the regulation of cell death pathways including apoptosis and necrosis [9, 10]. An elevated intracellular calcium concentration will hyperactivate calpains. The activation of calpains was shown to be involved in various pathological conditions, including ischemic brain injuries and chronic neurodegenerative diseases, for example, Alzheimer¡¯s disease [9, 11]. Previous
%U http://www.hindawi.com/journals/omcl/2013/367206/