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14 pages, 11386 KiB

Open AccessArticle

Association of a Disrupted Dipping Pattern of Blood Pressure with Progression of Renal Injury during the Development of Salt-Dependent Hypertension in Rats

by Abu Sufiun, Asadur Rahman, Kazi Rafiq, Yoshihide Fujisawa, Daisuke Nakano, Hideki Kobara, Tsutomu Masaki and Akira Nishiyama

Int. J. Mol. Sci. 2020, 21(6), 2248; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21062248 - 24 Mar 2020

Cited by 6 | Viewed by 2526

Abstract

The aim of the present study is to investigate whether a disruption of the dipping pattern of blood pressure (BP) is associated with the progression of renal injury in Dahl salt-sensitive (DSS) hypertensive rats. Seven-week-old DSS rats were fed a high salt diet [...] Read more.

The aim of the present study is to investigate whether a disruption of the dipping pattern of blood pressure (BP) is associated with the progression of renal injury in Dahl salt-sensitive (DSS) hypertensive rats. Seven-week-old DSS rats were fed a high salt diet (HSD; 8% NaCl) for 10 weeks, followed by a transition to a normal salt diet (NSD; 0.3% NaCl) for 4 weeks. At baseline, NSD-fed DSS rats showed a dipper-type circadian rhythm of BP. By contrast, HSD for 5 days caused a significant increase in the difference between the active and inactive periods of BP with an extreme dipper type of BP, while proteinuria and renal tissue injury were not observed. Interestingly, HSD feeding for 10 weeks developed hypertension with a non-dipper pattern of BP, which was associated with obvious proteinuria and renal tissue injury. Four weeks after switching to an NSD, BP and proteinuria were significantly decreased, and the BP circadian rhythm returned to the normal dipper pattern. These data suggest that the non-dipper pattern of BP is associated with the progression of renal injury during the development of salt-dependent hypertension. Full article

(This article belongs to the Special Issue Crosstalk between Circadian Rhythm and Diseases)

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22 pages, 614 KiB

Open AccessArticle

Circadian Gene Polymorphisms Associated with Breast Cancer Susceptibility

by Monika Lesicka, Ewa Jabłońska, Edyta Wieczorek, Beata Pepłońska, Jolanta Gromadzińska, Barbara Seroczyńska, Leszek Kalinowski, Jarosław Skokowski and Edyta Reszka

Int. J. Mol. Sci. 2019, 20(22), 5704; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20225704 - 14 Nov 2019

Cited by 18 | Viewed by 3177

Abstract

Breast cancer (BC) is a major problem for civilization, manifested by continuously increasing morbidity and mortality among women worldwide. Core circadian genes may play an important role in cancer development and progression. To evaluate the effects of single nucleotide polymorphism (SNP) in circadian [...] Read more.

Breast cancer (BC) is a major problem for civilization, manifested by continuously increasing morbidity and mortality among women worldwide. Core circadian genes may play an important role in cancer development and progression. To evaluate the effects of single nucleotide polymorphism (SNP) in circadian genes in BC risk, 16 functional SNPs were genotyped in 321 BC patients and 364 healthy women using the TaqMan fluorescence-labelled probes or High-Resolution Melt Curve technique in the Real-Time PCR system. The selected SNPs were analyzed for the risk of BC, progression, and the influence on gene expression in BC tissue pairs to demonstrate the functionality of genetic variants. The study showed a relationship between an increased BC risk under the dominant genetic model of CRY2 rs10838524, PER2 rs934945, and recessive genetic model of PER1 rs2735611. A protective effect of BMAL1 rs2279287 was observed among carriers with at least one variant allele. Moreover, we found an increased risk of estrogen-/progesterone-positive tumors under the dominant genetic model of PER2 rs934945 and estrogen negative tumors under the variant genotype of CRY2 rs10838524, PER1 rs2735611. We demonstrated significantly altered gene expression of BMAL1, CRY2, PER1, PER2, PER3 according to particular genotypes in the BC tissue pairs. Our findings support the hypothesized role of circadian genes in breast carcinogenesis and indicate probable biomarkers for breast cancer susceptibility. Full article

(This article belongs to the Special Issue Crosstalk between Circadian Rhythm and Diseases)

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17 pages, 3861 KiB

Open AccessArticle

The Mechanisms Underlying the Cytotoxic Effects of Copper Via Differentiated Embryonic Chondrocyte Gene 1

by Ssu-Yu Chen, Shu-Ting Liu, Wun-Rong Lin, Chi-Kang Lin and Shih-Ming Huang

Int. J. Mol. Sci. 2019, 20(20), 5225; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20205225 - 22 Oct 2019

Cited by 15 | Viewed by 3952

Abstract

Copper is an essential trace element within cells, but it also exerts cytotoxic effects through induction of reactive oxygen species (ROS) production. To determine the mechanisms underlying copper-induced ROS production, we examined the effects of copper sulfate in HeLa cells. Exposure to copper [...] Read more.

Copper is an essential trace element within cells, but it also exerts cytotoxic effects through induction of reactive oxygen species (ROS) production. To determine the mechanisms underlying copper-induced ROS production, we examined the effects of copper sulfate in HeLa cells. Exposure to copper sulfate led to dose-dependent decreases in HeLa cell viability, along with increases in the subG1 and G2/M populations and corresponding decreases in the G1 population. Copper sulfate also increased the levels of apoptosis, senescence, mitochondrial dysfunction, autophagy, ROS, and the expression of several stress proteins, including ATF3, c-Fos, DEC1 (differentiated embryonic chondrocyte gene 1), p21, p53, and HIF-1α (hypoxia-inducible factor 1 alpha). The suppression of copper-induced ROS generation by the ROS scavenger N-acetyl cysteine verified copper’s functional role, while the suppression of copper’s effects by the copper chelator disulfiram, confirmed its specificity. Selective induction of HIF-1α, p53, and phosphorylated ERK proteins by copper was blocked by the knockdown of the transcription factor DEC1, suggesting copper’s effects are mediated by DEC1. In addition to HeLa cells, copper also exerted cytotoxic effects in human endometrial (HEC-1-A) and lung (A549) adenocarcinoma cells, but not in normal human kidney (HEK293) or bronchial (Beas-2B) epithelial cells. These findings shed new light on the functional roles of copper within cells. Full article

(This article belongs to the Special Issue Crosstalk between Circadian Rhythm and Diseases)

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16 pages, 6756 KiB

Open AccessArticle

Dec1 Deficiency Suppresses Cardiac Perivascular Fibrosis Induced by Transverse Aortic Constriction

by Hue Thi Le, Fuyuki Sato, Akira Kohsaka, Ujjal K. Bhawal, Tomomi Nakao, Yasuteru Muragaki and Masanori Nakata

Int. J. Mol. Sci. 2019, 20(19), 4967; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20194967 - 08 Oct 2019

Cited by 13 | Viewed by 4739

Abstract

Cardiac fibrosis is a major cause of cardiac dysfunction in hypertrophic hearts. Differentiated embryonic chondrocyte gene 1 (Dec1), a basic helix–loop–helix transcription factor, has circadian expression in the heart; however, its role in cardiac diseases remains unknown. Therefore, using Dec1 knock-out [...] Read more.

Cardiac fibrosis is a major cause of cardiac dysfunction in hypertrophic hearts. Differentiated embryonic chondrocyte gene 1 (Dec1), a basic helix–loop–helix transcription factor, has circadian expression in the heart; however, its role in cardiac diseases remains unknown. Therefore, using Dec1 knock-out (Dec1KO) and wild-type (WT) mice, we evaluated cardiac function and morphology at one and four weeks after transverse aortic constriction (TAC) or sham surgery. We found that Dec1KO mice retained cardiac function until four weeks after TAC. Dec1KO mice also revealed more severely hypertrophic hearts than WT mice at four weeks after TAC, whereas no significant change was observed at one week. An increase in Dec1 expression was found in myocardial and stromal cells of TAC-treated WT mice. In addition, Dec1 circadian expression was disrupted in the heart of TAC-treated WT mice. Cardiac perivascular fibrosis was suppressed in TAC-treated Dec1KO mice, with positive immunostaining of S100 calcium binding protein A4 (S100A4), alpha smooth muscle actin (αSMA), transforming growth factor beta 1 (TGFβ1), phosphorylation of Smad family member 3 (pSmad3), tumor necrosis factor alpha (TNFα), and cyclin-interacting protein 1 (p21). Furthermore, Dec1 expression was increased in myocardial hypertrophy and myocardial infarction of autopsy cases. Taken together, our results indicate that Dec1 deficiency suppresses cardiac fibrosis, preserving cardiac function in hypertrophic hearts. We suggest that Dec1 could be a new therapeutic target in cardiac fibrosis. Full article

(This article belongs to the Special Issue Crosstalk between Circadian Rhythm and Diseases)

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Review

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13 pages, 696 KiB

Open AccessReview

Crosstalk Among Circadian Rhythm, Obesity and Allergy

by Kanami Orihara, Atsushi Haraguchi and Shigenobu Shibata

Int. J. Mol. Sci. 2020, 21(5), 1884; https://doi.org/10.3390/ijms21051884 - 10 Mar 2020

Cited by 19 | Viewed by 5248

Abstract

The circadian clock system works not only as a cellular time-keeper but also as a coordinator for almost all physiological functions essential to maintaining human health. Therefore, disruptions or malfunctions of this system can cause many diseases and pre-symptomatic conditions. Indeed, previous studies [...] Read more.

The circadian clock system works not only as a cellular time-keeper but also as a coordinator for almost all physiological functions essential to maintaining human health. Therefore, disruptions or malfunctions of this system can cause many diseases and pre-symptomatic conditions. Indeed, previous studies have indicated that disrupted clock gene expression rhythm is closely related to obesity, and that allergic diseases can be regulated by controlling peripheral clocks in organs and tissues. Moreover, recent studies have found that obesity can lead to immune disorders. Accordingly, in this review, we assess the connection between obesity and allergy from the point of view of the circadian clock system anew and summarize the relationships among the circadian clock system, obesity, and allergy. Full article

(This article belongs to the Special Issue Crosstalk between Circadian Rhythm and Diseases)

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19 pages, 1192 KiB

Open AccessReview

Circadian Clock, Time-Restricted Feeding and Reproduction

by Xiaoyue Pan, Meredith J. Taylor, Emma Cohen, Nazeeh Hanna and Samantha Mota

Int. J. Mol. Sci. 2020, 21(3), 831; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21030831 - 28 Jan 2020

Cited by 27 | Viewed by 6393

Abstract

The goal of this review was to seek a better understanding of the function and differential expression of circadian clock genes during the reproductive process. Through a discussion of how the circadian clock is involved in these steps, the identification of new clinical [...] Read more.

The goal of this review was to seek a better understanding of the function and differential expression of circadian clock genes during the reproductive process. Through a discussion of how the circadian clock is involved in these steps, the identification of new clinical targets for sleep disorder-related diseases, such as reproductive failure, will be elucidated. Here, we focus on recent research findings regarding circadian clock regulation within the reproductive system, shedding new light on circadian rhythm-related problems in women. Discussions on the roles that circadian clock plays in these reproductive processes will help identify new clinical targets for such sleep disorder-related diseases. Full article

(This article belongs to the Special Issue Crosstalk between Circadian Rhythm and Diseases)

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19 pages, 1247 KiB

Open AccessReview

Molecular Interactions between Pathogens and the Circadian Clock

by Sailen Barik

Int. J. Mol. Sci. 2019, 20(23), 5824; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20235824 - 20 Nov 2019

Cited by 12 | Viewed by 5051

Abstract

The daily periodicity of the Earth’s rotation around the Sun, referred to as circadian (Latin “circa” = about, and “diem” = day), is also mirrored in the behavior and metabolism of living beings. The discovery that dedicated cellular genes control various aspects of [...] Read more.

The daily periodicity of the Earth’s rotation around the Sun, referred to as circadian (Latin “circa” = about, and “diem” = day), is also mirrored in the behavior and metabolism of living beings. The discovery that dedicated cellular genes control various aspects of this periodicity has led to studies of the molecular mechanism of the circadian response at the cellular level. It is now established that the circadian genes impact on a large network of hormonal, metabolic, and immunological pathways, affecting multiple aspects of biology. Recent studies have extended the role of the circadian system to the regulation of infection, host–pathogen interaction, and the resultant disease outcome. This critical review summarizes our current knowledge of circadian-pathogen interaction at both systemic and cellular levels, but with emphasis on the molecular aspects of the regulation. Wherever applicable, the potential of a direct interaction between circadian factors and pathogenic macromolecules is also explored. Finally, this review offers new directions and guidelines for future research in this area, which should facilitate progress. Full article

(This article belongs to the Special Issue Crosstalk between Circadian Rhythm and Diseases)

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12 pages, 291 KiB

Open AccessReview

The Role of the Molecular Clock in Promoting Skeletal Muscle Growth and Protecting against Sarcopenia

by Jacopo A. Vitale, Matteo Bonato, Antonio La Torre and Giuseppe Banfi

Int. J. Mol. Sci. 2019, 20(17), 4318; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20174318 - 03 Sep 2019

Cited by 29 | Viewed by 5965

Abstract

The circadian clock has a critical role in many physiological functions of skeletal muscle and is essential to fully understand the precise underlying mechanisms involved in these complex interactions. The importance of circadian expression for structure, function and metabolism of skeletal muscle is [...] Read more.

The circadian clock has a critical role in many physiological functions of skeletal muscle and is essential to fully understand the precise underlying mechanisms involved in these complex interactions. The importance of circadian expression for structure, function and metabolism of skeletal muscle is clear when observing the muscle phenotype in models of molecular clock disruption. Presently, the maintenance of circadian rhythms is emerging as an important new factor in human health, with disruptions linked to ageing, as well as to the development of many chronic diseases, including sarcopenia. Therefore, the aim of this review is to present the latest findings demonstrating how circadian rhythms in skeletal muscle are important for maintenance of the cellular physiology, metabolism and function of skeletal muscle. Moreover, we will present the current knowledge about the tissue-specific functions of the molecular clock in skeletal muscle. Full article

(This article belongs to the Special Issue Crosstalk between Circadian Rhythm and Diseases)

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