title: Release of mitochondrial Opa1 following oxidative stress in HT22 cells.
abstract: Cellular mechanisms involved in multiple neurodegenerative diseases converge on mitochondria to induce overproduction of reactive oxygen species, damage to mitochondria, and subsequent cytochrome c release. Little is currently known regarding the contribution mitochondrial dynamics play in cytochrome c release following oxidative stress in neurodegenerative disease. Here we induced oxidative stress in the HT22 cell line with glutamate and investigated key mediators of mitochondrial dynamics to determine the role this process may play in oxidative stress induced neuronal death. We report that glutamate treatment in HT22 cells induces increase in reactive oxygen species (ROS), release of the mitochondrial fusion protein Opa1 into the cytosol, with concomitant release of cytochrome c. Furthermore, following the glutamate treatment alterations in cell signaling coincide with mitochondrial fragmentation which culminates in significant cell death in HT22 cells. Finally, we report that treatment with the antioxidant tocopherol attenuates glutamate induced-ROS increase, release of mitochondrial Opa1 and cytochrome c, and prevents cell death.
authors.affiliation: Department of Emergency Medicine, Wayne State University School of Medicine, 550 E. Canfield, Detroit, MI, USA; Cardiovascular Research Institute, Wayne State University School of Medicine, 540 E. Canfield, Detroit, MI, USA; Department of Physiology, Wayne State University School of Medicine, 550 E. Canfield, Detroit, MI, USA.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Sanderson
authors.affiliation: Department of Emergency Medicine, Wayne State University School of Medicine, 550 E. Canfield, Detroit, MI, USA.
authors.forename: Sarita
authors.initials: S
authors.lastname: Raghunayakula
authors.affiliation: Department of Emergency Medicine, Wayne State University School of Medicine, 550 E. Canfield, Detroit, MI, USA; Cardiovascular Research Institute, Wayne State University School of Medicine, 540 E. Canfield, Detroit, MI, USA; Department of Physiology, Wayne State University School of Medicine, 550 E. Canfield, Detroit, MI, USA. Electronic address: rkumar@med.wayne.edu.
authors.forename: Rita
authors.initials: R
authors.lastname: Kumar
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002460:Cell Line; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress; D024505:Tocopherols / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D020558:GTP Phosphohydrolases; C498809:Opa1 protein, mouse; D024505:Tocopherols
keywords: Cytochrome c; Glutamate; HT22; Mitochondrial dynamics: mitochondria; Neurodegeneration; Oxidative stress