Impairment of heme biosynthesis induces short circadian period in body temperature rhythms in mice.
Impairment of heme biosynthesis induces short circadian period in body temperature rhythms in mice.
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血红素生物合成受损会导致小鼠体温节律缩短。
DOI：
10.1152/ajpregu.00019.2011
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发表时间：
2012
期刊：
影响因子：
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通讯作者：
Mitsumoto A.
中科院分区：
文献类型：
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作者：
Iwadate R;Satoh Y;Watanabe Y;Kawai H;Kudo N;Kawashima Y;Mashino T;Mitsumoto A.
哺乳动物生物钟基因转录本的功能在体外已经被证明是由血红素结合所控制的。为了研究血红素对体内生物节律的影响，我们测量了运动活性（LA）和核心体温（Tb）的卟啉症小鼠模型与血红素生物合成受损喂养小鼠含灰黄霉素（GF）的饮食。在光暗循环（12 h：12 h）条件下，喂食含2.0%GF饲料（GF 2.0）的小鼠Tbor LA的生物节律分别在1-3 h出现短暂的时相提前或类时相提前现象（均P< 0.05）。在持续黑暗条件下，小鼠的昼夜节律周期也有短暂的缩短，缩短了约0.3h（P< 0.01）。有趣的是，观察到的持续时间异常的昼夜节律在GF2.0小鼠持续1和3周之间的发病后的GF摄入，这一发现与血红素生物合成受损的程度。当我们检查急性卟啉症治疗药物、血红素和高渗葡萄糖对GF 2.0小鼠病理状态的影响时，发现腹腔内给予血红素（10 mg·kg-1·day-1）或葡萄糖（9 g·kg-1·day-1）7天可部分逆转（50%）与急性卟啉症相关的尿δ-氨基乙酰丙酸水平升高。血红素处理抑制了GF2.0小鼠昼夜节律中的相位提前（P< 0.05），并恢复了血红素的减少（P< 0.01），而葡萄糖处理则无此作用。这些结果表明，血红素生物合成的障碍，特别是血红素的减少，可能会影响动物的昼夜节律的相位和周期。
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 (Tb) 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 Tbor 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 Tbrhythms 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.