Diurnal oscillations of endogenous H2O2 sustained by p66Shc regulate circadian clocks

Pei, Jian-Fei; Li, Xun-Kai; Li, Wenqi; Gao, Qian; Zhang, Yang; Wang, Xiaoman; Fu, Jiaqi; Cui, Shen-Shen; Qu, Jia-Hua; Zhao, Xiang; Hao, Dejun; Ju, Dapeng; Liu, Na; Carroll, Kate S.; Yang, Jing; Zhang, Eric Erquan; Cao, Ji‐Min; Chen, Hou-Zao; Liu, De-Pei

doi:10.1038/s41556-019-0420-4

Cited by 98 publications

(101 citation statements)

References 73 publications

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“…Thus, intracellular ROS generation is tightly regulated from various sources via antioxidant defense molecules of cells [ 87 ]. The circadian system plays a fundamental role in controlling cellular function [ 88 ], and redox homeostasis is regulated by the circadian clock [ 89 ]. Bmal1 and/or Nrf2 plays a key role in circadian expression of antioxidant genes and ROS homeostasis [ 4 ].…”

Section: Discussionmentioning

confidence: 99%

Clock Protein Bmal1 and Nrf2 Cooperatively Control Aging or Oxidative Response and Redox Homeostasis by Regulating Rhythmic Expression of Prdx6

Chhunchha

Kubo

Singh

2020

Cells

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Many disorders of aging, including blinding-diseases, are associated with deficiency of brain and muscle arnt-like protein 1 (Bmal1) and, thereby, dysregulation of antioxidant-defense pathway. However, knowledge is limited regarding the role of Bmal1 regulation of antioxidant-pathway in the eye lens/lens epithelial cells (LECs) at the molecular level. We found that, in aging human (h)LECs, a progressive decline of nuclear factor erythroid 2-related factor 2 (Nrf2)/ARE (antioxidant response element)-mediated antioxidant genes was connected to Bmal1-deficiency, leading to accumulation of reactive oxygen species (ROS) and cell-death. Bmal1-depletion disrupted Nrf2 and expression of its target antioxidant genes, like Peroxiredoxin 6 (Prdx6). DNA binding and transcription assays showed that Bmal1 controlled expression by direct binding to E-Box in Prdx6 promoter to regulate its transcription. Mutation at E-Box or ARE reduced promoter activity, while disruption of both sites diminished the activity, suggesting that both sites were required for peak Prdx6-transcription. As in aging hLECs, ROS accumulation was increased in Bmal1-deficient cells and the cells were vulnerable to death. Intriguingly, Bmal1/Nrf2/Prdx6 and PhaseII antioxidants showed rhythmic expression in mouse lenses in vivo and were reciprocally linked to ROS levels. We propose that Bmal1 is pivotal for regulating oxidative responses. Findings also reveal a circadian control of antioxidant-pathway, which is important in combating lens/LECs damage induced by aging or oxidative stress.

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Section: Discussionmentioning

confidence: 99%

Clock Protein Bmal1 and Nrf2 Cooperatively Control Aging or Oxidative Response and Redox Homeostasis by Regulating Rhythmic Expression of Prdx6

Chhunchha

Kubo

Singh

2020

Cells

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“…However, feeding-associated hormones and metabolites, as well as metabolic and redox states, have been suggested to convey nutritional information to circadian clocks. For example, fluctuations in nicotinamide adenine dinucleotide (NAD + ) cofactors and endogenous H 2 O 2 are sensed by the molecular clock machinery, thereby regulating circadian rhythmicity [94,95]. Moreover, the NAD + sensing protein deacetylase SIRT1 regulates the magnitude of clock gene expression in the periphery [96][97][98].…”

Section: Non-photic Entrainment Of Peripheral Clocksmentioning

confidence: 99%

Coupled network of the circadian clocks: a driving force of rhythmic physiology

2020

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The circadian system is composed of coupled endogenous oscillators that allow living beings, including humans, to anticipate and adapt to daily changes in their environment. In mammals, circadian clocks form a hierarchically organized network with a ‘master clock’ located in the suprachiasmatic nucleus of the hypothalamus, which ensures entrainment of subsidiary oscillators to environmental cycles. Robust rhythmicity of body clocks is indispensable for temporally coordinating organ functions, and the disruption or misalignment of circadian rhythms caused for instance by modern lifestyle is strongly associated with various widespread diseases. This review aims to provide a comprehensive overview of our current knowledge about the molecular architecture and system‐level organization of mammalian circadian oscillators. Furthermore, we discuss the regulatory roles of peripheral clocks for cell and organ physiology and their implication in the temporal coordination of metabolism in human health and disease. Finally, we summarize methods for assessing circadian rhythmicity in humans.

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“…Indeed, oxidative stress can drive the expression of REV-ERBα, which in turn regulates the expression of antioxidant transcription factor forkhead box protein O-1 (FOXO1) as well as stimulates autophagy and mitochondrial biogenesis [ 142 ]. Circadian oscillation of H 2 O 2 level is observed in mammalian cells and mouse liver, and can directly regulate CLOCK circadian function via cysteine oxidation [ 143 ]. Moreover, nicotinamide adenine dinucleotide (NAD) has been recently recognized as a “metabolic oscillator” that displays circadian oscillations and is the missing-link between energy metabolism and circadian control [ 144 , 145 , 146 ].…”

Section: Oxidative Stress and Circadian Rhythmmentioning

confidence: 99%

Circadian Rhythm in Adipose Tissue: Novel Antioxidant Target for Metabolic and Cardiovascular Diseases

Man¹,

Xia²,

Li³

2020

Antioxidants

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Obesity is a major risk factor for most metabolic and cardiovascular disorders. Adipose tissue is an important endocrine organ that modulates metabolic and cardiovascular health by secreting signaling molecules. Oxidative stress is a common mechanism associated with metabolic and cardiovascular complications including obesity, type 2 diabetes, and hypertension. Oxidative stress can cause adipose tissue dysfunction. Accumulating data from both humans and experimental animal models suggest that adipose tissue function and oxidative stress have an innate connection with the intrinsic biological clock. Circadian clock orchestrates biological processes in adjusting to daily environmental changes according to internal or external cues. Recent studies have identified the genes and molecular pathways exhibiting circadian expression patterns in adipose tissue. Disruption of the circadian rhythmicity has been suggested to augment oxidative stress and aberrate adipose tissue function and metabolism. Therefore, circadian machinery in the adipose tissue may be a novel therapeutic target for the prevention and treatment of metabolic and cardiovascular diseases. In this review, we summarize recent findings on circadian rhythm and oxidative stress in adipose tissue, dissect the key components that play a role in regulating the clock rhythm, oxidative stress and adipose tissue function, and discuss the potential use of antioxidant treatment on metabolic and cardiovascular diseases by targeting the adipose clock.

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Diurnal oscillations of endogenous H2O2 sustained by p66Shc regulate circadian clocks

Cited by 98 publications

References 73 publications

Clock Protein Bmal1 and Nrf2 Cooperatively Control Aging or Oxidative Response and Redox Homeostasis by Regulating Rhythmic Expression of Prdx6

Clock Protein Bmal1 and Nrf2 Cooperatively Control Aging or Oxidative Response and Redox Homeostasis by Regulating Rhythmic Expression of Prdx6

Coupled network of the circadian clocks: a driving force of rhythmic physiology

Circadian Rhythm in Adipose Tissue: Novel Antioxidant Target for Metabolic and Cardiovascular Diseases

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