Prothymosin-alpha plays a defensive role in retinal ischemia through necrosis and apoptosis inhibition.
Prothymosin-alpha (ProTalpha) causes a switch in cell death mode from necrosis to neurotrophin-reversible apoptosis in primary cultured cortical neurons. In the present study, post-ischemic administration (3 or 24 h, intravenously) of recombinant mouse ProTalpha without neurotrophins completely prevented ischemia-induced retinal damage accompanying necrosis and apoptosis, as well as dysfunction assessed by electroretinogram. Treatments with anti-erythropoietin (EPO) or brain-derived neurotrophic factor (BDNF) immunoglobulin G (IgG) reversed ProTalpha-induced inhibition of apoptosis. ProTalpha upregulated retinal EPO and BDNF levels in the presence of ischemia. Moreover, intravitreous administration of anti-ProTalpha IgG or an antisense oligodeoxynucleotide for ProTalpha accelerated ischemia-induced retinal damage. We also observed that ischemia treatment caused a depletion of ProTalpha from retinal cells. Altogether, these results suggest that the systemic administration of ProTalpha switches ischemia-induced necrosis to apoptosis, which in turn is inhibited by neurotrophic factors upregulated by ProTalpha and ischemia. ProTalpha released upon ischemic stress was found to have a defensive role in retinal ischemia.
Fujita
R
R
Division of Molecular Pharmacology and Neuroscience, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Ueda
M
M
Fujiwara
K
K
Ueda
H
H
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage / Q000494:pharmacology; D017209:Apoptosis; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D004921:Erythropoietin / Q000378:metabolism; D007511:Ischemia / Q000473:pathology*; D008297:Male; D051379:Mice; D009336:Necrosis; D011498:Protein Precursors / Q000502:physiology*; D015427:Reperfusion Injury / Q000517:prevention & control; D012160:Retina / Q000378:metabolism; D012171:Retinal Vessels / Q000473:pathology*; D013947:Thymosin / Q000031:analogs & derivatives* / Q000502:physiology
D000906:Antibodies; D019208:Brain-Derived Neurotrophic Factor; D011498:Protein Precursors; C040782:prothymosin alpha; D004921:Erythropoietin; D013947:Thymosin