Diurnal-and sex-related difference of metallothionein expression in mice

Zhang, Dan; Jin, Taiyi; Xu, Yiqiao; Lu, Yuan‐Fu; Wu, Qin; Zhang, Yu-Kun Jennifer; Liu, Jie

doi:10.1186/1740-3391-10-5

Cited by 20 publications

(21 citation statements)

References 29 publications

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“…Cry1 showed a 13-fold difference between nadir and peak in females and 23-fold in males. There was basically no sex difference in circadian variation of Cry1, except for slightly higher expression in males at 22:00 h. For the antiphase clock gene Bmal1, there was a 14-fold difference in females and 54-fold in males, and females had higher mRNA levels than males at 10:00 and 2:00 h. We have examined the expression of six clock genes in our recent publications (Xu et al, 2012; Zhang et al, 2009, 2011, 2012), and the oscillation patterns observed in C57 mice are similar in KM mice and represent typical circadian rhythms, thus validating further analysis of the Cyp genes.…”

Section: Resultsmentioning

confidence: 99%

“…Special analysis of circadian rhythms followed the method of Refinetti et al (2007), as described in our recent publications (Xu et al, 2012; Zhang et al, 2012). Sex difference at the same time point was analyzed by Student’s t test.…”

Section: Methodsmentioning

confidence: 99%

“…However, little is known about the sex differences in the circadian variation of Cyp genes. We have shown circadian and sex dimorphism of hepatic antioxidant components, including the Nrf2 and glutathione systems, the enzymatic and non-enzymatic antioxidant genes in normal mouse liver (Xu et al, 2012), as well as diurnal and sex variations of metallothionein-1 and -2 in mouse liver, kidney, and blood (Zhang et al, 2012). The present study further aimed to examine the sex differences in the circadian variation of major xenobiotic-metabolizing CYP enzymes (Cyp1–4 families) and CYP enzymes responsible for bile acid synthesis (Cyp7a1 and Cyp27a1).…”

Section: Introductionmentioning

confidence: 99%

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Sex Differences in the Circadian Variation of Cytochrome P450 Genes and Corresponding Nuclear Receptors in Mouse Liver

Jin

et al. 2013

Chronobiology International

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Sex differences and circadian variation are two major factors that affect the expression of drug-processing genes. This study aimed to examine sex differences in the circadian variation of hepatic cytochrome P450 (Cyp) genes and corresponding nuclear receptors. Adult mice were acclimated to environmentally controlled facilities for 2 wks, and livers were collected every 4 h during a 24-h period. Total RNA and protein were isolated and subjected to real-time reverse transcriptase–polymerase chain reaction (RT-PCR) and Western blot analysis. The mRNA expression of the aryl hydrocarbon receptor (AhR) and AhR-regulated Cyp1a1 and Cyp1a2 were higher in females and higher during the light phase. The mRNA expression of constitutive and rostane receptor (CAR) and CYP2B10 protein was female-predominant and higher in the dark phase. Pregnane X receptor (PXR) peaked around 18:00 h, but PXR-regulated Cyp3a11 and Cyp3a25 were higher at 10:00 h, without apparent sex dimorphism at protein levels. Peroxisome proliferator-activated receptor-a (PPARα), Cyp4a10, and Cyp4a14 were higher in females and peaked between 14:00 and 18:00 h. The mRNA levels of farnesoid X receptor (FXR), Cyp7a1, and Cyp27a1 peaked around 18:00 h and CYP7A1 protein was higher during the dark phase and higher in females. Cyp7b1(male-predominant) and Cyp2a4 (female-predominant) both showed circadian variation. Circadian variation of hepatic clock genes such as nuclear receptor Rev-erbα, cryptochrome 1 (Cry1), and brain muscle ARNT-like protein 1 (Bmal1) showed distinct patterns. Sex differences and circadian rhythmicity of Cyp genes and corresponding nuclear receptors exist in mouse liver that could impact xenobiotic metabolism and toxicity at different times of the day.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Sex Differences in the Circadian Variation of Cytochrome P450 Genes and Corresponding Nuclear Receptors in Mouse Liver

Jin

et al. 2013

Chronobiology International

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“…Diurnal variation of hepatic detoxification enzyme genes. Many antioxidant enzyme genes display diurnal variations, such as the Nrf2 detoxication pathway genes [30], enzymatic detoxication components such as superoxide dismutase (SOD), catalase, glutathione peroxidase (GSH-Px1) and non-enzymatic protein such as metallothionein (MT) [31]. GSH is low in the afternoon which is partially responsible for acetaminophen hepatotoxicity when given in the afternoon [23].…”

Section: Diurnal Variation Of Hepatic Uptake Transportersmentioning

confidence: 99%

Circadian Clock Gene Expression and Drug/Toxicant Interactions as Novel Targets of Chronopharmacology and Chronotoxicology

Liu¹,

Li²,

Xu³

et al. 2018

Circadian Rhythm - Cellular and Molecular Mechanisms

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Circadian rhythms are driven and maintained by circadian clock gene networks in both brain and peripheral organs. In the liver, circadian rhythms produce oscillation in drug Phase-I, Phase-II, and Phase-III (transporters) metabolism genes, which in turn would affect drug disposition and detoxication, resulting in diurnal variations of efficacy and toxicity when drugs are given at different times of the day. On the other hand, drugs and toxicants could affect circadian clock gene expression to produce biological effects leading to therapeutic or toxic outcomes. This chapter reviewed the relevant literature and a dozen of publications from our work, discussed the interactions of circadian clock genes with drugs and/or toxicants to better understand the importance of circadian clock gene expression as novel targets in Pharmacology and Toxicology.

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“…In the liver this is functionally important and may explain the decreased acetaminophen hepatotoxicity during the light/sleep phase [190]. Interestingly, hepatic metallothionein levels peak at the beginning of the active period, which may afford some level of enhanced antioxidant defense at this time [191]. …”

Section: Integration Of Mitochondrial Function Autophagy and Circmentioning

confidence: 99%

Redox biology and the interface between bioenergetics, autophagy and circadian control of metabolism

Wende

Young

Chatham

et al. 2016

Free Radical Biology and Medicine

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Understanding molecular mechanisms that underlie the recent emergence of metabolic diseases such as diabetes and heart failure has revealed the need for a multi-disciplinary research integrating the key metabolic pathways which change the susceptibility to environmental or pathologic stress. At the physiological level these include the circadian control of metabolism which aligns metabolism with temporal demand. The mitochondria play an important role in integrating the redox signals and metabolic flux in response to the changing activities associated with chronobiology, exercise and diet. At the molecular level this involves dynamic post-translational modifications regulating transcription, metabolism and autophagy. In this review we will discuss different examples of mechanisms which link these processes together. An important pathway capable of linking signaling to metabolism is the post-translational modification of proteins by O-linked N-acetylglucosamine (O-GlcNAc). This is a nutrient regulated protein modification that plays an important role in impaired cellular stress responses. Circadian clocks have also emerged as critical regulators of numerous cardiometabolic processes, including glucose/lipid homeostasis, hormone secretion, redox status and cardiovascular function. Central to these pathways are the response of autophagy, bioenergetics to oxidative stress, regulated by Keap1/Nrf2 and mechanisms of metabolic control. The extension of these ideas to the emerging concept of bioenergetic health will be discussed.

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Diurnal-and sex-related difference of metallothionein expression in mice

Cited by 20 publications

References 29 publications

Sex Differences in the Circadian Variation of Cytochrome P450 Genes and Corresponding Nuclear Receptors in Mouse Liver

Sex Differences in the Circadian Variation of Cytochrome P450 Genes and Corresponding Nuclear Receptors in Mouse Liver

Circadian Clock Gene Expression and Drug/Toxicant Interactions as Novel Targets of Chronopharmacology and Chronotoxicology

Redox biology and the interface between bioenergetics, autophagy and circadian control of metabolism

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