title: Mitochondrial-mediated suppression of ROS production upon exposure of neurons to lethal stress: mitochondrial targeted preconditioning.
abstract: Preconditioning represents the condition where transient exposure of cells to an initiating event leads to protection against subsequent, potentially lethal stimuli. Recent studies have established that mitochondrial-centered mechanisms are important mediators in promoting development of the preconditioning response. However, many details concerning these mechanisms are unclear. The purpose of this review is to describe the initiating and subsequent intracellular events involving mitochondria which can lead to neuronal preconditioning. These mitochondrial specific targets include: 1) potassium channels located on the inner mitochondrial membrane; 2) respiratory chain enzymes; and 3) oxidative phosphorylation. Following activation of mitochondrial ATP-sensitive potassium (mitoK(ATP)) channels and/or increased production of reactive oxygen species (ROS) resulting from the disruption of the respiratory chain or during energy substrate deprivation, morphological changes or signaling events involving protein kinases confer immediate or delayed preconditioning on neurons that will allow them to survive otherwise lethal insults. While the mechanisms involved are not known with certainty, the results of preconditioning are the enhanced neuronal viability, the attenuated influx of intracellular calcium, the reduced availability of ROS, the suppression of apoptosis, and the maintenance of ATP levels during and following stress.
authors.affiliation: Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Winston-Salem, NC NC 27157-1010, USA. dbusija@wfubmc.edu
authors.forename: David W
authors.initials: DW
authors.lastname: Busija
authors.forename: Tamas
authors.initials: T
authors.lastname: Gaspar
authors.forename: Ferenc
authors.initials: F
authors.lastname: Domoki
authors.forename: Prasad V
authors.initials: PV
authors.lastname: Katakam
authors.forename: Ferenc
authors.initials: F
authors.lastname: Bari
mesh_terms: D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D001578:Benzopyrans / Q000494:pharmacology; D002545:Brain Ischemia / Q000378:metabolism / Q000517:prevention & control*; D016923:Cell Death / Q000502:physiology; D004579:Electron Transport / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D015640:Ion Channel Gating; D019194:Ischemic Preconditioning; D054086:KATP Channels / Q000502:physiology; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000502:physiology; D008928:Mitochondria / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D010085:Oxidative Phosphorylation; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors*
chemical_list: C428117:BMS 191095; D001562:Benzimidazoles; D001578:Benzopyrans; D007093:Imidazoles; D054086:KATP Channels; D051036:Large-Conductance Calcium-Activated Potassium Channels; D017382:Reactive Oxygen Species; C086491:NS 1619