Impairment of heme biosynthesis induces short circadian period in body temperature rhythms in mice

Reiko Iwadate, Yoko Satoh, Yukino Watanabe, Hiroshi Kawai, Naomi Kudo, Yoichi Kawashima, Tadahiko Mashino, Atsushi Mitsumoto

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

It has been demonstrated that the function of mammalian clock gene transcripts is controlled by the binding of heme in vitro. To examine the effects of heme on biological rhythms in vivo, we measured locomotor activity (LA) and core body temperature (T b) in a mouse model of porphyria with impaired heme biosynthesis by feeding mice a griseofulvin (GF)-containing diet. Mice fed with a 2.0% GF-containing diet (GF2.0) transiently exhibited phase advance or phase advance-like phenomenon by 1-3 h in terms of the biological rhythms of T b or LA, respectively (both, P < 0.05) while mice were kept under conditions of a light/dark cycle (12 h:12 h). We also observed a transient, ~0.3 h shortening of the period of circadian T b rhythms in mice kept under conditions of constant darkness (P < 0.01). Interestingly, the observed duration of abnormal circadian rhythms in GF2.0 mice lasted between 1 and 3 wk after the onset of GF ingestion; this finding correlated well with the extent of impairment of heme biosynthesis. When we examined the effects of therapeutic agents for acute porphyria, heme, and hypertonic glucose on the pathological status of GF2.0 mice, it was found that the intraperitoneal administration of heme (10 mg·kg -1·day -1) or glucose (9 g·kg -1·day -1) for 7 days partially reversed (50%) increases in urinary δ-aminolevulinic acids levels associated with acute porphyria. Treatment with heme, but not with glucose, suppressed the phase advance (-like phenomenon) in the diurnal rhythms (P < 0.05) and restored the decrease of heme (P < 0.01) in GF2.0 mice. These results suggest that impairments of heme biosynthesis, in particular a decrease in heme, may affect phase and period of circadian rhythms in animals.

Original languageEnglish
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume303
Issue number1
DOIs
Publication statusPublished - 2012 Jul 1

Fingerprint

Body Temperature
Heme
Griseofulvin
Circadian Rhythm
Acute Intermittent Porphyria
Periodicity
Locomotion
Glucose
Diet
Porphyrias
Aminolevulinic Acid
Darkness
Photoperiod
Therapeutic Uses
Eating

Keywords

  • δ-aminolevulinic acid
  • Core body temperature
  • Phase advance
  • Porphyria
  • Resting temperature

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Impairment of heme biosynthesis induces short circadian period in body temperature rhythms in mice. / Iwadate, Reiko; Satoh, Yoko; Watanabe, Yukino; Kawai, Hiroshi; Kudo, Naomi; Kawashima, Yoichi; Mashino, Tadahiko; Mitsumoto, Atsushi.

In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology, Vol. 303, No. 1, 01.07.2012.

Research output: Contribution to journalArticle

Iwadate, Reiko ; Satoh, Yoko ; Watanabe, Yukino ; Kawai, Hiroshi ; Kudo, Naomi ; Kawashima, Yoichi ; Mashino, Tadahiko ; Mitsumoto, Atsushi. / Impairment of heme biosynthesis induces short circadian period in body temperature rhythms in mice. In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology. 2012 ; Vol. 303, No. 1.
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