Intermittent hypoxia induces time-dependent changes in the protein kinase B signaling pathway in the hippocampal CA1 region of the rat.
Intermittent hypoxia (IH) during sleep induces temporally defined increases in apoptosis within vulnerable brain regions such as the hippocampal CA1 region in rats. Protein kinase B (AKT) has emerged as major signal transduction protein underlying inhibition of apoptosis and consequent increases in cell survival. Sprague Dawley adult male rats were exposed during sleep to IH or to normoxia (RA) for periods ranging from 0 to 30 days, and expression of total and phosphorylated AKT, of forkhead family members FKHR and FKHRL1, and of glycogen synthase kinase 3beta (GSK3beta) was assessed. Decreases in phosphorylation occurred as early as 1 h IH exposure, reached a nadir at 6 h-3 days, and then progressively returned to baseline levels at 14-30 days. Phosphorylated AKT and GSK3beta were intensely expressed and highly colocalized within neuronal cells (Neu-N positive) in the CA1 region. Thus, IH induces time-dependent biphasic changes in AKT survival pathways within the CA1 region that are temporally correlated with the initial increases and subsequent decreases in neuronal apoptosis.
Goldbart
Aviv
A
Kosair Children's Hospital Research Institute, Department of Pediatrics, University of Louisville, Louisville, KY 40202, USA.
Cheng
Zixi Jack
ZJ
Brittian
Kenneth R
KR
Gozal
David
D
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000502:physiology; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006624:Hippocampus / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D002534:Hypoxia, Brain / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009410:Nerve Degeneration / Q000201:enzymology* / Q000503:physiopathology; D009419:Nerve Tissue Proteins; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time; D015398:Signal Transduction / Q000502:physiology; D012891:Sleep Apnea Syndromes / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism; D000071161:Forkhead Box Protein O1
D004268:DNA-Binding Proteins; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D038362:Glycogen Synthase Kinase 3; D000071679:Glycogen Synthase Kinase 3 beta; D009419:Nerve Tissue Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D014157:Transcription Factors; C499515:FOXO3 protein, rat; C074639:Foxo1 protein, rat; D000071161:Forkhead Box Protein O1; C494920:Akt1 protein, rat; C000605508:Gsk3b protein, rat