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

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.

• Authors: Reiko Iwadate, Yoko Satoh, Yukino Watanabe, Hiroshi Kawai, Naomi Kudo, Yoichi Kawashima, Tadahiko Mashino, Atsushi Mitsumoto
• Journal: American journal of physiology. Regulatory, integrative and comparative physiology (Am J Physiol Regul Integr Comp Physiol) Vol. 303 Issue 1 Pg. R8-18 (Jul 01 2012) ISSN: 1522-1490 [Electronic] United States
• PMID: 22552790 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Griseofulvin
• Heme
• Glucose

Topics

• Animals
• Body Temperature (drug effects, physiology)
• Circadian Rhythm (drug effects, physiology)
• Disease Models, Animal
• Glucose (pharmacology)
• Griseofulvin (adverse effects, pharmacology)
• Heme (metabolism, pharmacology)
• Locomotion (drug effects, physiology)
• Male
• Mice
• Mice, Inbred ICR
• Porphyrias (chemically induced, metabolism, physiopathology)