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Thymosin-β4 Attenuates Ethanol-induced Neurotoxicity in Cultured Cerebral Cortical Astrocytes by Inhibiting Apoptosis

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Abstract

Thymosin-β4 (Tβ4) 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 Tβ4 is also involved in challenges with external stress such as ethanol-induced neurotoxicity. In the present study, we investigated the effects of Tβ4 on ethanol-induced neurotoxicity in cultured cerebral cortical astrocytes and the underlying mechanisms. Primarily cultured astrocytes were treated with 1 μg/ml Tβ4 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. Tβ4 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 Tβ4 attenuates ethanol-induced neurotoxicity in cultured cortical astrocytes through inhibition of apoptosis signaling, and one of the mechanisms underlying the capacity of Tβ4 to suppress apoptosis may in part be due to its effect of anti-peroxidation.

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Acknowledgments

This work was supported by the Natural Science Foundation of China (30872829, 30571998) and Chinese PLA national scientific technological project (06G089).

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  1. Institute of Neurosciences, The Fourth Military Medical University, 710032, Xi’an, China

    Hao Yang, Xi-Ying Jiao, Jian Wang, Gong Ju & Si-Wei You

  2. Department of Radiology, Tangdu Hospital, The Fourth Military Medical University, 710038, Xi’an, China

    Guang-Bin Cui

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  1. Hao Yang
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Correspondence to Gong Ju or Si-Wei You.

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Yang, H., Cui, GB., Jiao, XY. et al. Thymosin-β4 Attenuates Ethanol-induced Neurotoxicity in Cultured Cerebral Cortical Astrocytes by Inhibiting Apoptosis. Cell Mol Neurobiol 30, 149–160 (2010). https://doi.org/10.1007/s10571-009-9439-6

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