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Novel neuroprotective action of prothymosin alpha‐derived peptide against retinal and brain ischemic damages
Author(s) -
Halder Sebok Kumar,
Matsunaga Hayato,
Yamaguchi Haruka,
Ueda Hiroshi
Publication year - 2013
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.12132
Subject(s) - neuroprotection , ischemia , pharmacology , in vivo , retina , brain ischemia , retinal , apoptosis , biology , medicine , endocrinology , neuroscience , biochemistry , microbiology and biotechnology
Prothymosin alpha (ProTα), a nuclear protein, is implicated in the inhibition of ischemia‐induced necrosis as well as apoptosis in the brain and retina. Although ProTα has multiple biological functions through distinct regions in its sequence, it has remained which region is involved in this neuroprotection. This study reported that the active core peptide sequence P 30 (amino acids 49–78) of ProTα exerts its full survival effect in cultured cortical neurons against ischemic stress. Our in vivo study revealed that intravitreous administration of P 30 at 24 h after retinal ischemia significantly blocks the ischemia‐induced functional damages of retina at day 7. In addition, P 30 completely rescued the retinal ischemia‐induced ganglion cell damages at day 7 after the ischemic stress, along with partial blockade of the loss of bipolar, amacrine, and photoreceptor cells. On the other hand, intracerebroventricular (3 nmol) or systemic (1 mg/kg; i.v.) injection of P 30 at 1 h after cerebral ischemia (1 h tMCAO ) significantly blocked the ischemia‐induced brain damages and disruption of blood vessels. Systemic P 30 delivery (1 mg/kg; i.v.) also significantly ameliorated the ischemic brain caused by photochemically induced thrombosis. Taken together, this study confers a precise demonstration about the novel protective activity of ProTα‐derived small peptide P 30 against the ischemic damages in vitro and in vivo .