The effect of hypoxia and catecholamines on regional expression of heat-shock protein-72 mRNA in neonatal piglet brain.
The present study has shown that hypoxia leads to expression of heat-shock protein in the brain of newborn piglets and this process is almost completely abolished by depletion of catecholamines prior to the hypoxic episode. The piglets were anesthetized and mechanically ventilated. One hour of hypoxia was generated by decreasing the oxygen fraction in the inspired gas (FiO2) from 22% to 6%-10%. FiO2 was then returned to the control value for a period of 2 h. Following the 2 h of reoxygenation, regional expression of the 72-kDa heat-shock protein (hsp72) mRNA was determined using in situ hybridization and autoradiography. The hypoxic insult (cortical pO2 = 3-10 mmHg) induced expression of hsp72 mRNA in regions of both white and gray matter, with strong expression occurring in the cerebral cortex of individual animals. Depleting the brain of catecholamines prior to hypoxia, by treating the animals with alpha-methyl-p-tyrosine (AMT), resulted in a major change in the hsp72 mRNA expression. In the catecholamine depleted group of animals, the intensity of hsp72 mRNA expression was greatly decreased or almost completely abolished relative to the nondepleted hypoxic group. These results suggest that the catecholamines play a significant role in the expression of the hsp72 gene in response to hypoxic insult in neonatal brain.
Murphy
S J
SJ
Department of Biochemistry and Biophysics, Medical School, University of Pennsylvania, Philadelphia 19104, USA.
Song
D
D
Welsh
F A
FA
Wilson
D F
DF
Pastuszko
A
A
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D002534:Hypoxia, Brain / Q000378:metabolism*; D017403:In Situ Hybridization; D008781:Methyltyrosines / Q000494:pharmacology*; D010100:Oxygen / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D012016:Reference Values; D013552:Swine; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D014446:Tyrosine 3-Monooxygenase / Q000037:antagonists & inhibitors*; D019805:alpha-Methyltyrosine
D004791:Enzyme Inhibitors; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D008781:Methyltyrosines; D012333:RNA, Messenger; D019805:alpha-Methyltyrosine; D014446:Tyrosine 3-Monooxygenase; D010100:Oxygen