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Published July 4, 2003 | Published
Journal Article Open

p38 Mitogen-activated Protein Kinase Regulates Oscillation of Chick Pineal Circadian Clock

Abstract

Extracellular signal-regulated kinase (ERK) and p38 are members of the mitogen-activated protein kinase (MAPK) family, and in some cases these kinases serve for closely related cellular functions within a cell. In a wide range of animal clock structures, ERK plays an important role in the circadian time-keeping mechanism. Here we found that immunoreactivity to p38 protein was uniformly distributed among cells in the chick pineal gland. On the other hand, a constant level of activated p38 was detected over the day, predominantly in the follicular and parafollicular pinealocytes that are potential circadian clock-containing cells. Chronic application of SB203580, a selective and reversible inhibitor of p38, to the cultured chick pineal cells markedly lengthened the period of the circadian rhythm of the melatonin release (up to 28.7 h). Noticeably, despite no significant temporal change of activated p38 level, a 4-h pulse treatment with SB203580 delayed the phase of the rhythm only when delivered during the subjective day. These results indicate a time-of-day-specific role of continuously activated p38 in the period length regulation of the chick pineal clock and suggest temporally separated regulation of the clock by two MAPKs, nighttime-activated ERK and daytime-working p38.

Additional Information

© 2003 the American Society for Biochemistry and Molecular Biology. Received for publication, December 13, 2002, and in revised form, April 23, 2003. Originally published In Press as doi:10.1074/jbc.M212726200 on April 28, 2003. We thank Dr. Toshiyuki Okano for insightful discussion. This work was supported in part by grants-in-aid from the Japanese Ministry of Education, Culture, Sports, Science and Technology. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Both authors [Y.H. and K.S.] contributed equally to this work. [T.H. was] Supported by Research Fellowships of the Japan Society for the Promotion of Science for Young Scientists.

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August 22, 2023
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