Microgravity decreases tyrosine hydroxylase expression in rat adrenals.
During spaceflight, alterations in blood and urinary catecholamine (CA) levels have been observed, yet the cellular/molecular mechanisms leading to these changes are not known. We used molecular, immunological, and biochemical approaches to analyze in situ the expression of catecholamine enzymes in adrenal medullary chromaffin cells of rats flown for 6 days on board Space Shuttle mission STS-54. Exposure to microgravity (10(-6) g) resulted in a 35% inhibition of both the expression and the specific activity of tyrosine hydroxylase (TH), the rate-limiting step in the cascade of CA synthesis. By contrast, the expression, specific activity, and immunoreactivity of other catecholamine-synthesizing enzymes, e.g., phenylethanolamine-N-methyl-transferase (PNMT), were not altered. The total tissue CA contents were reduced, concomitant with a decrease in the epinephrine:norepinephrine ratio. These results are in line with reports of other gravity-sensitive cellular effects and suggest that the inhibition of TH expression might be due to a direct effect of microgravity on PKC-dependent signal transduction pathways in chromaffin cells.
Department of Medicine, University of Wisconsin Medical School, Milwaukee 53201.
P I
PI
Lelkes
E M
EM
Ramos
D M
DM
Chick
J
J
Liu
B R
BR
Unsworth
D000311:Adrenal Glands / Q000201:enzymology*; D000818:Animals; D001483:Base Sequence; D002395:Catecholamines / Q000096:biosynthesis / Q000378:metabolism; D017931:DNA Primers; D004299:Dopamine beta-Hydroxylase / Q000235:genetics / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D066298:In Vitro Techniques; D008297:Male; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D010625:Phenylethanolamine N-Methyltransferase / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis* / Q000235:genetics; D014893:Weightlessness
D002395:Catecholamines; D017931:DNA Primers; D009838:Oligodeoxyribonucleotides; D014446:Tyrosine 3-Monooxygenase; D004299:Dopamine beta-Hydroxylase; D010625:Phenylethanolamine N-Methyltransferase