Role of glutathione metabolism and apoptosis in the regression of liver hemopoiesis.
Although apoptosis has been believed to play important roles in ontogenic development of animals, the molecular mechanism that triggers the regression of liver hemopoiesis during perinatal period is not known. Apoptosis is induced by many factors, such as decrease in growth factors and increased oxygen stress. Because hepatic gamma-glutamyltransferase (GGT) changes markedly during the perinatal period of a rodent, metabolism of glutathione (GSH), a naturally occurring major antioxidant, might change significantly in and around liver cells. To know the possible involvement of apoptosis and GSH metabolism in the regression of hemopoiesis, hepatocytes and hemopoietic cells were isolated from fetal rat liver. Biochemical analysis revealed that, during the perinatal period, hepatic GGT levels transiently increased predominantly with hepatocytes, suggesting a marked change in thiol status in and around these cells. Cell culture analysis revealed that hemopoietic cells but not hepatocytes exhibited a marked apoptosis in a thiol-free medium, as judged from DNA fragmentation. The apoptosis of hemopoietic cells was inhibited by various thiols, such as L-cysteine, N-acetyl-L-cysteine (NAC), and GSH. These observations suggested that a marked change in GSH status in and around liver cells might play critical roles in triggering apoptosis of hemopoietic cells, thereby enhancing the regression of liver hemopoiesis.
Yamamasu
S
S
Department of Biochemistry, Osaka City University Medical School, Japan.
Sato
E F
EF
Ogita
S
S
Inoue
M
M
D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D005260:Female; D005865:Gestational Age; D005914:Globins / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D008099:Liver / Q000166:cytology / Q000196:embryology / Q000201:enzymology / Q000378:metabolism*; D009929:Organ Size; D011247:Pregnancy; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012156:Reticulocytes / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000378:metabolism; D001613:beta 2-Microglobulin / Q000378:metabolism; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D012333:RNA, Messenger; D013438:Sulfhydryl Compounds; D001613:beta 2-Microglobulin; D005914:Globins; D004247:DNA; D005723:gamma-Glutamyltransferase; D019009:Proto-Oncogene Proteins c-kit; D005978:Glutathione