Heat-induced inhibition of superoxide dismutase and accumulation of reactive oxygen species leads to HT-22 neuronal cell death

✍ Scribed by Naglaa F. El-Orabi; Colin B. Rogers; Heather Gray Edwards; Dean D. Schwartz

• Publisher: Elsevier Science
• Year: 2011
• Tongue: English
• Weight: 582 KB
• Volume: 36
• Category: Article
• ISSN: 0306-4565
• DOI: 10.1016/j.jtherbio.2010.11.002

✦ Synopsis

Superoxide dismutase (SOD) is major cytosolic antioxidant enzyme responsible for dismutation of superoxide anion (O dÀ 2 ). Alterations in SOD expression and activity are associated with various neurological disorders. In the present study, we utilized neuronal HT-22 cells to investigate heatstressed induced cytotoxicity. Heat stress at 43 1C for 30 min caused a decrease in SOD-1 mRNA levels, cytoplasmic SOD protein and enzyme activity and a corresponding decline in cell number during a 48 h recovery at 371C. During the recovery phase, there was an increase in reactive oxygen species generation and an increase in NADPH oxidase activity with a corresponding increase in DNA fragmentation and release of cytochrome c from the mitochondria. The increase in ROS accumulation and cell death was abolished by pretreatment with the SOD mimetics EUK-134 and Mn(III)TBAP and the NADPH oxidase inhibitor apocynin. These data suggest that hyperthermia increases ROS generation by increasing NADPH activity and decreasing SOD activity leading to cytotoxicity in HT-22 cells.