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Hypoxia affects expression of circadian genes PER1 and CLOCK in mouse brain
Author(s) -
Chilov Dmitri,
Hofer Thomas,
Bauer Christian,
Wenger Roland H.,
Gassmann Max
Publication year - 2001
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.01-0092com
Subject(s) - per1 , circadian rhythm , biology , clock , gene isoform , microbiology and biotechnology , circadian clock , protein subunit , medicine , endocrinology , gene , genetics
The key elements of circadian clockwork and oxygen homeostasis are the PAS protein family members PER and CLOCK and hypoxia‐inducible factor 1α (HIF‐1α). The PAS domain serves as an interface for protein‐protein interactions. We asked whether a cross‐talk exists between the PAS components of hy‐poxic and circadian pathways. We found several iso‐forms of PER1 protein that exhibit tissue‐specific size differences. In the mouse brain, a predominantly nuclear 48 kDa isoform that followed a daily rhythm was observed. The 48 kDa form was found in the nuclear fractions derived from mouse liver, Swiss3T3 fibro‐blasts, and N2A neuroblastoma cells. In mouse kidney and human 293 kidney cells, a 55 kDa PER1 form was detected. CLOCK was observed as a predicted 100 kDa protein in rat‐1 cells and in all analyzed mouse tissues including brain, liver, kidney, and spleen. In contrast to PER1, CLOCK protein expression was not rhythmic. Exposure to hypoxia led to increased PER1 and CLOCK protein levels in mice. Based on coimmuno‐precipitation experiments that showed protein‐protein interaction between PER1 and the a subunit of HIF‐1, we suggest that these hypoxic effects may be modulated by HIF‐1α.—Chilov, D., Hofer, T., Bauer, C., Wenger, R. H., Gassmann, M. Hypoxia affects expression of circadian genes PER1 and CLOCK in mouse brain. FASEB J. 15, 2613–2622 (2001)