title: Thymosin-beta4 attenuates ethanol-induced neurotoxicity in cultured cerebral cortical astrocytes by inhibiting apoptosis.
abstract: Thymosin-beta4 (Tbeta4) is a major actin monomer-binding peptide in mammalian tissues and plays a crucial role in the nervous system in synaptogenesis, neuronal survival and migration, axonal growth, and plastic changes of dendritic spines. However, it is unknown whether Tbeta4 is also involved in challenges with external stress such as ethanol-induced neurotoxicity. In the present study, we investigated the effects of Tbeta4 on ethanol-induced neurotoxicity in cultured cerebral cortical astrocytes and the underlying mechanisms. Primarily cultured astrocytes were treated with 1 microg/ml Tbeta4 2 h prior to administration of 100 mM ethanol for 0.5, 1, 3 and 6 days, respectively. The results showed that ethanol caused neurotoxicity in cultured astrocytes, as shown by declined cell viability, distinct astroglial apoptosis and increased intracellular peroxidation. Tbeta4 markedly promoted cell viability, ameliorated the injury of intracellular glial fibrillary acidic protein-immunopositive cytoskeletal structures, reduced the percentage of apoptotic astrocyte and cellular DNA fragmentation, suppressed caspase-3 activity and upregulated Bcl-2 expression, inhibited the accumulation of reactive oxygen species and production of malondialdehyde in ethanol-treated astrocytes in a time-dependent manner. These data indicated that Tbeta4 attenuates ethanol-induced neurotoxicity in cultured cortical astrocytes through inhibition of apoptosis signaling, and one of the mechanisms underlying the capacity of Tbeta4 to suppress apoptosis may in part be due to its effect of anti-peroxidation.
authors.affiliation: Institute of Neurosciences, The Fourth Military Medical University, 710032, Xi'an, China. yanghao71_99@yahoo.com
authors.forename: Hao
authors.initials: H
authors.lastname: Yang
authors.forename: Guang-Bin
authors.initials: GB
authors.lastname: Cui
authors.forename: Xi-Ying
authors.initials: XY
authors.lastname: Jiao
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Gong
authors.initials: G
authors.lastname: Ju
authors.forename: Si-Wei
authors.initials: SW
authors.lastname: You
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001253:Astrocytes / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology*; D053148:Caspase 3 / Q000378:metabolism; D002452:Cell Count; D002467:Cell Nucleus / Q000187:drug effects / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000473:pathology*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D000431:Ethanol; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D020258:Neurotoxicity Syndromes / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013947:Thymosin / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects; D000099201:Thymosin beta(4)
chemical_list: D053148:Caspase 3; D003598:Cytoskeletal Proteins; D000431:Ethanol; D005904:Glial Fibrillary Acidic Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D013947:Thymosin; D000099201:Thymosin beta(4)
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