Transcriptional Control of Antioxidant Defense by the Circadian Clock

Patel, Sonal; Velingkaar, Nikkhil; Kondratov, Roman V.

doi:10.1089/ars.2013.5671

Cited by 71 publications

(52 citation statements)

References 80 publications

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“…Mean 6 SEM; (*) P < 0.05; (**) P < 0.01, t-test. (Stangherlin and Reddy 2013;Patel et al 2014). However, the underlying clock-controlled molecular mechanisms and their role in tissue-specific physiology are still poorly understood.…”

Section: Discussionmentioning

confidence: 99%

“…cofactors, as shown for the transcription factor BMAL1 (Rey et al 2011), or post-transcriptional processing (Patel et al 2014). The difference in the timing of maximal expression may be necessary for the specific function of individual NRF2 targets.…”

Section: Rhythmic Promoter Binding Of Nrf2 Drives Oscillations Of Arementioning

confidence: 96%

“…Daily changes in the environment (cycles in light/darkness, feeding, rest-activity, and temperature fluctuations) inevitably expose the mammalian cells and tissues to periodic challenges, including oxidative insults from environmental toxins/pollutants and endogenously produced reactive metabolites as products of respiration (Patel et al 2014). Failure to scavenge reactive oxygen species (ROS), reactive nitrogen species (RNS), and reactive electrophiles results in excessive oxidative stress, leading to damage to critical macromolecules and cellular structures (Veal et al 2007).…”

mentioning

confidence: 99%

“…The ability to anticipate and withstand such cyclic insults (e.g., through effective ROS scavenging) is therefore essential for normal protective tissue functions. There is emerging evidence that circadian clocks regulate processes that keep ROS at physiological levels and protect organisms from oxidative stress (Stangherlin and Reddy 2013;Patel et al 2014). Indeed, self-sustained rhythms in the cellular redox state (Kondratov et al 2006;O'Neil et al 2011;Edgar et al 2012;Wang et al 2012) as well as ROSresponsive antioxidant genes (Geyfman et al 2012;Lai et al 2012) have been observed in the brain and/or peripheral tissues.…”

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confidence: 99%

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The circadian clock regulates rhythmic activation of the NRF2/glutathione-mediated antioxidant defense pathway to modulate pulmonary fibrosis

et al. 2014

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The disruption of the NRF2 (nuclear factor erythroid-derived 2-like 2)/glutathione-mediated antioxidant defense pathway is a critical step in the pathogenesis of several chronic pulmonary diseases and cancer. While the mechanism of NRF2 activation upon oxidative stress has been widely investigated, little is known about the endogenous signals that regulate the NRF2 pathway in lung physiology and pathology. Here we show that an E-boxmediated circadian rhythm of NRF2 protein is essential in regulating the rhythmic expression of antioxidant genes involved in glutathione redox homeostasis in the mouse lung. Using an in vivo bleomycin-induced lung fibrosis model, we reveal a clock ''gated'' pulmonary response to oxidative injury, with a more severe fibrotic effect when bleomycin was applied at a circadian nadir in NRF2 levels. Timed administration of sulforaphane, an NRF2 activator, significantly blocked this phenotype. Moreover, in the lungs of the arrhythmic Clock D19 mice, the levels of NRF2 and the reduced glutathione are constitutively low, associated with increased protein oxidative damage and a spontaneous fibrotic-like pulmonary phenotype. Our findings reveal a pivotal role for the circadian control of the NRF2/glutathione pathway in combating oxidative/fibrotic lung damage, which might prompt new chronotherapeutic strategies for the treatment of human lung diseases, including idiopathic pulmonary fibrosis.

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Section: Discussionmentioning

confidence: 99%

Section: Rhythmic Promoter Binding Of Nrf2 Drives Oscillations Of Arementioning

confidence: 96%

mentioning

confidence: 99%

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confidence: 99%

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The circadian clock regulates rhythmic activation of the NRF2/glutathione-mediated antioxidant defense pathway to modulate pulmonary fibrosis

et al. 2014

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“…It is for this reason that cataract is one of the iconic non-cancer consequences of IR damage (26) . This coupled to the fact that both oxidative defence mechanisms (27) and the repair of X-ray induced double strand breaks (DSBs) in DNA (28) are synchronized by circadian rhythms also means that the timing of radiotherapy and radioimaging procedures needs to be coordinated as we enter personalized medicine.…”

Section: Diurnal Changes In the Eye Lens: Cell Proliferation Melatonmentioning

confidence: 99%

The Impact of Circadian Rhythms on Medical Imaging and Radiotherapy Regimes for the Paediatric Patient

Forssell-Aronsson

Quinlan

2016

Radiation Protection Dosimetry

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Mechanisms for Tuning Engineered Nanomaterials to Enhance Radiation Therapy of Cancer

et al. 2020

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Engineered nanomaterials that produce reactive oxygen species on exposure to X‐ and gamma‐rays used in radiation therapy offer promise of novel cancer treatment strategies. Similar to photodynamic therapy but suitable for large and deep tumors, this new approach where nanomaterials acting as sensitizing agents are combined with clinical radiation can be effective at well‐tolerated low radiation doses. Suitably engineered nanomaterials can enhance cancer radiotherapy by increasing the tumor selectivity and decreasing side effects. Additionally, the nanomaterial platform offers therapeutically valuable functionalities, including molecular targeting, drug/gene delivery, and adaptive responses to trigger drug release. The potential of such nanomaterials to be combined with radiotherapy is widely recognized. In order for further breakthroughs to be made, and to facilitate clinical translation, the applicable principles and fundamentals should be articulated. This review focuses on mechanisms underpinning rational nanomaterial design to enhance radiation therapy, the understanding of which will enable novel ways to optimize its therapeutic efficacy. A roadmap for designing nanomaterials with optimized anticancer performance is also shown and the potential clinical significance and future translation are discussed.

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Transcriptional Control of Antioxidant Defense by the Circadian Clock

Cited by 71 publications

References 80 publications

The circadian clock regulates rhythmic activation of the NRF2/glutathione-mediated antioxidant defense pathway to modulate pulmonary fibrosis

The circadian clock regulates rhythmic activation of the NRF2/glutathione-mediated antioxidant defense pathway to modulate pulmonary fibrosis

The Impact of Circadian Rhythms on Medical Imaging and Radiotherapy Regimes for the Paediatric Patient

Mechanisms for Tuning Engineered Nanomaterials to Enhance Radiation Therapy of Cancer

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