Hypoxia induces major effects on cell cycle kinetics and protein expression in Drosophila melanogaster embryos.
Hypoxia induces a stereotypic response in Drosophila melanogaster embryos: depending on the time of hypoxia, embryos arrest cell cycle activity either at metaphase or just before S phase. To understand the mechanisms underlying hypoxia-induced arrest, two kinds of experiments were conducted. First, embryos carrying a kinesin-green fluorescent protein construct, which permits in vivo confocal microscopic visualization of the cell cycle, showed a dose-response relation between O2 level and cell cycle length. For example, mild hypoxia (Po2 approximately 55 Torr) had no apparent effect on cell cycle length, whereas severe hypoxia (Po2 approximately 25-35 Torr) or anoxia (Po2 = 0 Torr) arrested the cell cycle. Second, we utilized Drosophila embryos carrying a heat shock promoter driving the string (cdc25) gene (HS-STG3), which permits synchronization of embryos before the start of mitosis. Under conditions of anoxia, we induced a stabilization or an increase in the expression of several G1/S (e.g., dE2F1, RBF2) and G2/M (e.g., cyclin A, cyclin B, dWee1) proteins. This study suggests that, in fruit fly embryos, 1) there is a dose-dependent relationship between cell cycle length and O2 levels in fruit fly embryos, and 2) stabilized cyclin A and E2F1 are likely to be the mediators of hypoxia-induced arrest at metaphase and pre-S phase.
Douglas
R M
RM
Department of Pediatrics, Albert Einstein College of Medicine of Yeshiva University, New York, New York, USA.
Farahani
R
R
Morcillo
P
P
Kanaan
A
A
Xu
T
T
Haddad
G G
GG
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology*; D018797:Cell Cycle Proteins; D015687:Cell Hypoxia / Q000502:physiology*; D019925:Cyclin A / Q000502:physiology; D019926:Cyclin B / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D029721:Drosophila Proteins / Q000378:metabolism / Q000502:physiology; D004331:Drosophila melanogaster / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology*; D006360:Heat-Shock Proteins / Q000378:metabolism; D019476:Insect Proteins / Q000096:biosynthesis / Q000502:physiology*; D010100:Oxygen / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D012097:Repressor Proteins / Q000502:physiology; D013997:Time Factors; D014157:Transcription Factors / Q000502:physiology
D018797:Cell Cycle Proteins; C503698:CycB protein, Drosophila; D019925:Cyclin A; D019926:Cyclin B; D029721:Drosophila Proteins; C496298:E2f1 protein, Drosophila; D006360:Heat-Shock Proteins; D019476:Insect Proteins; C467582:RBF2 protein, Drosophila; D012097:Repressor Proteins; D014157:Transcription Factors; D017027:Protein Tyrosine Phosphatases; C059217:stg protein, Drosophila; D010100:Oxygen