Are changes in MAPK/ERK necessary or sufficient for entrainment in chick pineal cells?
Chick pineal cells in culture display a circadian rhythm of melatonin release. Light pulses can entrain (phase shift) the rhythm. One candidate for the photoentrainment pathway uses a mitogen-activated protein kinase (MAPK), also known as extracellular signal-regulated kinase (ERK). We tested the hypothesis that activation of ERK (by phosphorylation to p-ERK) is necessary and/or sufficient for entrainment by measuring the ability of several drugs, light, and other perturbations to change levels of p-ERK and to induce phase shifts in the melatonin rhythm. If changes in the levels of p-ERK are sufficient for photoentrainment, then all perturbations that reduce its level must induce light-like phase shifts, and all those that increase its level must induce dark-like phase shifts. If such changes are necessary for photoentrainment, then light pulses must reduce p-ERK levels, and the duration of the light pulse, the magnitude and duration of the change in p-ERK, and the size of the phase shift must correlate. We found five perturbations that reduced p-ERK levels. Of these, two induced light-like phase shifts (PD 98059 and caffeine), one induced dark-like phase shifts (SB203580), and two did not induce phase shifts at all (U0126 and omitting a medium change). Serum increased p-ERK levels without inducing any phase shifts. Finally, light pulses did not elicit changes in p-ERK, nor was there a diurnal rhythm in p-ERK levels, nor could rapid changes in p-ERK levels have accounted for duration effects of light pulses on phase shifts. Taken together, these results argue strongly against the hypothesis that reduction (or increases) in MAPK/ERK activation is necessary or sufficient for entrainment in chick pineal cells.
Yadav
Geetha
G
Laboratory of Cellular and Molecular Regulation, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892-4068, USA.
Straume
Martin
M
Heath
James
J
Zatz
Martin
M
D000121:Acetylserotonin O-Methyltransferase / Q000378:metabolism; D000818:Animals; D001798:Blood Proteins / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology; D002478:Cells, Cultured; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D002645:Chickens; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D003624:Darkness; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D008027:Light; D008550:Melatonin / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009994:Osmolar Concentration; D010870:Pineal Gland / Q000166:cytology / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D011725:Pyridines / Q000494:pharmacology
D001798:Blood Proteins; D000697:Central Nervous System Stimulants; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007093:Imidazoles; D011725:Pyridines; D002110:Caffeine; D000121:Acetylserotonin O-Methyltransferase; D020928:Mitogen-Activated Protein Kinases; D008550:Melatonin; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one