Ethanol increases TIEG2-MAO B cell death cascade in the prefrontal cortex of ethanol-preferring rats.
Brain cell loss has been reported in subjects with alcoholism. However, the molecular mechanisms are unclear. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and monoamine oxidase B (MAO B) reportedly play a role in cellular dysfunction with regards to ethanol exposure. We have recently reported that GAPDH protein expression was increased in the brains of rats fed with ethanol. Furthermore, GAPDH interacts with the transcriptional activator, transforming growth factor-beta-inducible early gene 2 (TIEG2), to augment TIEG2-mediated MAO B activation, resulting in neuronal cell damage due to ethanol exposure. The current study investigates whether the TIEG2-MAO B cascade is also active in the brains of rats fed with ethanol. Ten ethanol-preferring rats were fed with a liquid diet containing ethanol, with increasing amounts of ethanol up to a final concentration of 6.4% representing a final diet containing 36% of calories for 28 days. Ten control rats were fed the liquid diet without ethanol. The expression of TIEG2 protein, MAO B mRNA levels, MAO B catalytic activity, and the levels of anti-apoptotic protein Bcl 2 and apoptotic protein caspase 3 were determined in the prefrontal cortex of the rats. Ethanol significantly increased protein levels of TIEG2, active caspase 3, MAO B mRNA and enzyme activity, but significantly decreased Bcl 2 protein expression compared to control rats. In summary, ethanol increases the TIEG2-MAO B brain cell death cascade in rat brains, suggesting that the TIEG2-MAO B pathway is a novel pathway for brain cell damage resulting from ethanol exposure, and may contribute to chronic alcohol-induced brain damage.
Ou
Xiao-Ming
XM
Division of Neurobiology & Behavioral Research, Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, 2500 N. State Street, Jackson, MS 39216, USA. xou@psychiatry.umsmed.edu
Johnson
Chandra
C
Lu
Deyin
D
Johnson
Shakevia
S
Paul
Ian A
IA
Austin
Mark C
MC
Iyo
Abiye H
AH
Miguel-Hidalgo
Jose Javier
JJ
Luo
Jia
J
Bell
Richard L
RL
Grunewald
Matthew
M
Wang
Junming
J
Sittman
Donald B
DB
D000428:Alcohol Drinking / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D000431:Ethanol / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D008995:Monoamine Oxidase / Q000096:biosynthesis*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000201:enzymology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D015534:Trans-Activators / Q000096:biosynthesis* / Q000235:genetics
C569356:KLF11 protein, rat; D015534:Trans-Activators; D000431:Ethanol; D008995:Monoamine Oxidase