Thymosin-beta4 attenuates ethanol-induced neurotoxicity in cultured cerebral cortical astrocytes by inhibiting apoptosis.
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.
Yang
Hao
H
Institute of Neurosciences, The Fourth Military Medical University, 710032, Xi'an, China. yanghao71_99@yahoo.com
Cui
Guang-Bin
GB
Jiao
Xi-Ying
XY
Wang
Jian
J
Ju
Gong
G
You
Si-Wei
SW
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)
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)
Exp Eye Res. 2002 Feb;74(2):293-9
11950239
Alcohol Clin Exp Res. 2000 Apr;24(4):512-8
10798588
Cytotechnology. 2006 Oct;52(2):87-97
19002867
J Neurochem. 1997 Jun;68(6):2451-7
9166739
Biochim Biophys Acta. 1993 Mar 10;1176(1-2):59-63
8452879
Adv Exp Med Biol. 1994;366:291-305
7771260
Alcohol Clin Exp Res. 1993 Feb;17(1):174-83
8452200
Alcohol Clin Exp Res. 1985 Jan-Feb;9(1):49-55
3887968
Exp Cell Res. 2004 Feb 1;293(1):175-83
14729067
Cell Adhes Commun. 2000 Jan;7(4):311-20
10714392
Ann Neurol. 1994 Nov;36(5):747-51
7979220
Science. 1993 Nov 19;262(5137):1274-7
8235659
Curr Opin Struct Biol. 2000 Dec;10(6):649-55
11114501
Neuroimmunomodulation. 1997 May-Jun;4(3):163-70
9500150
J Neurochem. 1996 Dec;67(6):2425-33
8931475
Brain Res. 1996 Aug 26;731(1-2):39-44
8883852
Brain Res. 2007 Oct 31;1178:28-37
17888892
Prog Neurobiol. 2000 Dec;62(6):649-71
10880854
Annu Rev Neurosci. 1999;22:511-39
10202547
Br J Ophthalmol. 2008 Jul;92(7):992-7
18480304
Nat Rev Drug Discov. 2004 Mar;3(3):205-14
15031734
Curr Eye Res. 2002 Apr;24(4):268-73
12324865
Free Radic Biol Med. 1990;9(4):315-25
2283087
Alcohol Drug Res. 1987;7(5-6):423-41
3304313
J Neuroimmunol. 1998 Feb;82(1):64-72
9526847
J Neurosci. 2003 Jul 2;23(13):5715-22
12843275
Arch Biochem Biophys. 2002 Dec 15;408(2):162-70
12464267
Exp Eye Res. 2001 May;72(5):605-8
11311052
J Neurochem. 1996 Sep;67(3):1259-67
8752134
Neuroscience. 2002;112(3):707-16
12074912
Alcohol Alcohol. 2005 May-Jun;40(3):163-71
15767272
J Biol Chem. 2008 Jan 18;283(3):1534-1544
17984099
Biochem Biophys Res Commun. 2007 Dec 28;364(4):731-6
17967441
Neuroreport. 1996 Jul 8;7(10):1613-6
8904767
Nature. 1999 Jun 3;399(6735):483-7
10365962
J Immunol Methods. 1983 Dec 16;65(1-2):55-63
6606682
Eur J Neurosci. 1999 Oct;11(10):3488-98
10564357
J Mol Neurosci. 1992;3(3):165-70
1627460
J Neurochem. 2002 Nov;83(3):601-12
12390522
Neurosci Lett. 2006 Jan 30;393(2-3):136-40
16257121
Neurochem Res. 2008 Nov;33(11):2269-80
18461449
Prog Neurobiol. 2004 Feb;72(2):111-27
15063528
Ann N Y Acad Sci. 2007 Sep;1112:219-24
17947590
J Neurochem. 1997 Dec;69(6):2484-93
9375681
Neurotoxicol Teratol. 1997 Mar-Apr;19(2):141-6
9136130
Invest Ophthalmol Vis Sci. 2004 Apr;45(4):1095-100
15037574
Redox Rep. 2001;6(6):351-62
11865975
Development. 1999 Apr;126(7):1365-74
10068630
J Cell Biol. 1998 Jul 27;142(2):485-97
9679146
Alcohol. 2001 Jan;23(1):1-8
11282445
Brain Res. 1985 Jun;356(2):187-215
3159464
J Histochem Cytochem. 1989 Feb;37(2):229-40
2642942
J Neurosci. 1999 Mar 15;19(6):1959-64
10066249
J Cell Biol. 1996 Apr;133(2):381-90
8609170
Alcohol Alcohol. 1992 May;27(3):219-26
1449557
J Neurosci. 1998 Jul 15;18(14):5311-21
9651214
Neurotoxicology. 2001 Oct;22(5):593-9
11770880
Neuroscience. 1999;90(4):1433-44
10338310
Int J Biochem Cell Biol. 2001 Mar;33(3):205-20
11311852
J Neurochem. 1993 Dec;61(6):2104-14
8245965
Neurochem Int. 2008 May;52(6):1061-7
18082912
Alcohol Res Health. 2001;25(3):175-84
11810955
Alcohol Clin Exp Res. 1993 Aug;17(4):877-81
8105712
J Neurochem. 1995 Dec;65(6):2561-70
7595552
Invest Ophthalmol Vis Sci. 2007 Jan;48(1):27-33
17197512