title: Temperature increase exacerbates apoptotic neuronal death in chemically-induced ischemia.
abstract: It is well-established that hyperthermia increases neuronal death and worsens stroke outcome. However, little is known about the mechanisms of how hyperthermia is involved in this neuronal death process. In the present study, we examined how temperature increase exacerbates neuronal death using a model of chemical ischemia. Chemical ischemia was induced by treating SH-SY5Y neuroblastoma cells with sodium azide and deoxyglucose. Temperature increase was treated by placing the cells at 37°C (control) and 41°C (experimental). Cell survival was determined by trypan blue assay and ATP levels were measured with ATP assay kits. Protein expression was detected by western blot. Treatment with sodium azide resulted in cell death in a dose-responsive manner. Increased temperature worsened the ATP depletion and cell volume shrinkage. Temperature increase also enhanced ER stress as demonstrated by the elevated level of phospho-eIF2α and C/EBP homologous protein (CHOP). Inhibition of CHOP expression significantly decreased sodium azide-induced neuronal death. In addition, the increased temperature intensified the activation of caspase-3, an apoptotic effector protease, and inhibition of capspase-3 significantly reduced cell death. These findings support that temperature increase worsened the neuronal death by depleting intracellular ATP, inducing ER stress response and activating apoptotic signal transduction.
authors.affiliation: School of Biological Science, Illinois State University, Normal, Illinois, USA.
authors.forename: Chunyan
authors.initials: C
authors.lastname: He
authors.forename: Ann
authors.initials: A
authors.lastname: Stroink
authors.forename: Laura
authors.initials: L
authors.lastname: Vogel
authors.forename: Chen Xu
authors.initials: CX
authors.lastname: Wang
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D061945:Caspase Inhibitors / Q000494:pharmacology; D045744:Cell Line, Tumor; D003847:Deoxyglucose / Q000633:toxicity; D004721:Endoplasmic Reticulum / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005110:Extracellular Space / Q000378:metabolism; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D007511:Ischemia / Q000139:chemically induced* / Q000201:enzymology / Q000473:pathology*; D015398:Signal Transduction; D019810:Sodium Azide / Q000633:toxicity; D013696:Temperature
chemical_list: D061945:Caspase Inhibitors; D000255:Adenosine Triphosphate; D019810:Sodium Azide; D003847:Deoxyglucose; D053148:Caspase 3