Akt1 suppresses radiation-induced germ cell apoptosis in vivo.
Radiation exposure is a well-characterized germ cell injury model leading to cell cycle arrest or apoptosis. The serine-threonine kinase, Akt1, has been implicated in inhibiting cell death induced by different stimuli including growth factor withdrawal, cell cycle discordance, DNA damage, and loss of cell adhesion. However, the in vivo relevance of this prosurvival pathway has not been explored in the testis. To evaluate a protective role for Akt1 in the testis in vivo, we examined the incidence of apoptosis in Akt1-deficient mice after radiation-induced germ cell injury. We found that Akt kinase activity increases in the testes of wild-type mice after ionizing radiation, and that loss of Akt1 results in an earlier onset of germ cell apoptosis and enhanced sensitivity of mitotic spermatogonia to ionizing radiation. At both the mRNA and protein level, neither Akt2 nor Akt3 expression were induced in the absence of Akt1. These data demonstrate an important survival function governed by Akt1 and, to a lesser extent, Akt2 in the survival of germ cells after radiation-induced testicular injury. In addition, the results point to a role for Fas ligand in the regulation of this response.
Rasoulpour
Teresa
T
Department of Pathology and Laboratory Medicine, Brown University, Providence, Rhode Island 02912, USA.
DiPalma
Kathryn
K
Kolvek
Branko
B
Hixon
Mary
M
D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D002588:Cesium Radioisotopes; D053222:Fas Ligand Protein; D015870:Gene Expression; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008938:Mitosis; D051057:Proto-Oncogene Proteins c-akt / Q000032:analysis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D015398:Signal Transduction / Q000528:radiation effects; D013094:Spermatozoa / Q000166:cytology* / Q000528:radiation effects*; D013737:Testis / Q000737:chemistry / Q000528:radiation effects; D048069:Tumor Necrosis Factors / Q000032:analysis / Q000235:genetics; D019014:fas Receptor / Q000032:analysis / Q000235:genetics
D002588:Cesium Radioisotopes; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D048069:Tumor Necrosis Factors; D019014:fas Receptor; D051057:Proto-Oncogene Proteins c-akt