title: Protective effect of Homer 1a against hydrogen peroxide-induced oxidative stress in PC12 cells.
abstract: Oxidative stress-induced cell damage is involved in many neurological diseases. Homer protein, as an important scaffold protein at postsynaptic density, regulates synaptic structure and function. Here, we reported that hydrogen peroxide (H(2)O(2)) induced the expression of Homer 1a. Down-regulation of Homer 1a with a specific small interfering RNA (siRNA) exacerbated H(2)O(2)-induced cell injury. Up-regulation of Homer 1a by lentivirus transfection did not affect the anti-oxidant activity, but significantly reduced the reactive oxygen species (ROS) production and lipid peroxidation after H(2)O(2)-induced oxidative stress. Overexpression of Homer 1a attenuated the loss of mitochondrial membrane potential (MMP) and ATP production induced by H(2)O(2), and subsequently inhibited mitochondrial dysfunction-induced cytochrome c release, increase of Bax/Bcl-2 ratio and caspase-9/caspase-3 activity. Furthermore, in the presence of BAPTA-AM, an intracellular free-calcium (Ca(2+)) chelator, overexpression of Homer 1a had no significant effects on H(2)O(2)-induced oxidative stress. These results suggest that Homer 1a has protective effects against H(2)O(2)-induced oxidative stress by reducing ROS accumulation and activation of mitochondrial apoptotic pathway, and these protective effects are dependent on the regulation of intracellular Ca(2+) homeostasis.
authors.affiliation: Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an, PR China.
authors.forename: Peng
authors.initials: P
authors.lastname: Luo
authors.forename: Tao
authors.initials: T
authors.lastname: Chen
authors.forename: Yongbo
authors.initials: Y
authors.lastname: Zhao
authors.forename: Haoxiang
authors.initials: H
authors.lastname: Xu
authors.forename: Kai
authors.initials: K
authors.lastname: Huo
authors.forename: Mingming
authors.initials: M
authors.lastname: Zhao
authors.forename: Yuefan
authors.initials: Y
authors.lastname: Yang
authors.forename: Zhou
authors.initials: Z
authors.lastname: Fei
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D000072233:Homer Scaffolding Proteins; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D016716:PC12 Cells; D051381:Rats; D014162:Transfection
chemical_list: D002352:Carrier Proteins; D000072233:Homer Scaffolding Proteins; D006861:Hydrogen Peroxide