This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Long-term stressful situations or heavy ethanol intake induces brain injury;however, the exact biochemical changes that take place in the brain cells/tissues are not yet clear. The long-term objective of this proposal is to understand mechanisms of stress- or ethanol-induced brain tissue injury and to seek its prevention. Transforming growth factor-beta-inducible early gene 2 (TIEG2) is reported to activate monoamine oxidase (MAO) and induce apoptosis. We have found that a cell stressor (dexamethasone;Dex) or ethanol (75 mM) increases TIEG2 expression and causes cell death. One potential pathway is through increasing MAO activity and subsequent reactive oxygen species (ROS) production because MAO is an enzyme that catalyzes the oxidation of monoamine neurotransmitters. The catalytic activity of MAO generates reactive oxygen (H2O2), which is a major intracellular ROS that causes cell toxicity. Therefore, the TIEG2 MAO pathway may be one of mechanisms to contribute stress- or ethanol-induced cell injury. In addition, an MAO B inhibitor (0.25 nM) reduces TIEG2-MAO expression, thus protecting cells from the harmful effects of ethanol. We hypothesize that stress (Dex) or ethanol induces expression of TIEG2, an MAO transcriptional activator. Secondly, we hypothesize that MAO inhibitors can protect against stress- or ethanol-induced brain cell injury by reducing the levels of ROS produced by the TIEG2-MAO cascade.