Therapeutic benefits of 9-amino acid peptide derived from prothymosin alpha against ischemic damages

Therapeutic benefits of 9-amino acid peptide derived from prothymosin alpha against ischemic damages
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DOI:
10.1016/j.peptides.2013.02.022
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发表时间:
2013-05-01
期刊:
影响因子:
3
通讯作者:
Ueda, Hiroshi
Ueda, Hiroshi
中科院分区:
医学3区
文献类型:
--
作者:
Halder, Sebok Kumar;Sugimoto, Junya;Ueda, Hiroshi

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Prothymosin alpha (ProT alpha), a nuclear protein, plays multiple functions including cell survival. Most recently, we demonstrated that the active 30-amino acid peptide sequence/P-30 (amino acids 49-78) in ProT alpha retains its substantial activity in neuroprotection in vitro and in vivo as well as in the inhibition of cerebral blood vessel damages by the ischemic stress in retina and brain. But, it has remained to identify the minimum peptide sequence in ProT alpha that retains neuroprotective activity. The present study using the experiments of alanine scanning suggested that any amino acid in 9-amino acid peptide sequence/P-9 (amino acids 52-60) of P-30 peptide is necessary for its survival activity of cultured rat cortical neurons against the ischemic stress. In the retinal ischemia-perfusion model, intravitreous injection of 13924 h after ischemia significantly inhibited the cellular and functional damages at day 7. On the other hand, 2,3,5-triphenyltetrazolium chloride (TTC) staining and electroretinogram assessment showed that systemic delivery with P-9 1 h after the cerebral ischemia (1 h tMCAO) significantly blocks the ischemia-induced brain damages. In addition, systemic P-9 delivery markedly inhibited the cerebral ischemia (tMCAO)-induced disruption of blood vessels in brain. Taken together, the present study provides a therapeutic importance of 9-amino acid peptide sequence against ischemic damages. (C) 2013 Elsevier Inc. All rights reserved.