Prothymosin alpha as robustness molecule against ischemic stress to brain and retina.
Following stroke or traumatic damage, neuronal death via both necrosis and apoptosis causes loss of functions, including memory, sensory perception, and motor skills. As necrosis has the nature to expand, while apoptosis stops the cell death cascade in the brain, necrosis is considered to be a promising target for rapid treatment for stroke. We identified the nuclear protein, prothymosin alpha (ProTalpha) from the conditioned medium of serum-free culture of cortical neurons as a key protein-inhibiting necrosis. In the culture of cortical neurons in the serum-free condition without any supplements, ProTalpha inhibited the necrosis, but caused apoptosis. In the ischemic brain or retina, ProTalpha showed a potent inhibition of both necrosis and apoptosis. By use of anti-brain-derived neurotrophic factor or anti-erythropoietin IgG, we found that ProTalpha inhibits necrosis, but causes apoptosis, which is in turn inhibited by ProTalpha-induced neurotrophins under the condition of ischemia. From the experiment using anti-ProTalpha IgG or antisense oligonucleotide for ProTalpha, it was revealed that ProTalpha has a pathophysiological role in protecting neurons in stroke.
Division of Molecular Pharmacology and Neuroscience, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. ueda@nagasaki-u.ac.jp
Hiroshi
H
Ueda
Hayato
H
Matsunaga
Hitoshi
H
Uchida
Mutsumi
M
Ueda
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism / Q000503:physiopathology; D017077:Culture Media, Conditioned / Q000378:metabolism; D004921:Erythropoietin / Q000378:metabolism; D007162:Immunoproteins / Q000378:metabolism; D007511:Ischemia / Q000378:metabolism; D009336:Necrosis / Q000378:metabolism; D009414:Nerve Growth Factors / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism*; D012160:Retina / Q000378:metabolism* / Q000503:physiopathology; D020521:Stroke / Q000378:metabolism; D013947:Thymosin / Q000031:analogs & derivatives* / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D017077:Culture Media, Conditioned; D007162:Immunoproteins; D009414:Nerve Growth Factors; D011498:Protein Precursors; C040782:prothymosin alpha; D004921:Erythropoietin; D013947:Thymosin