Daily Regulation of Phototransduction, Circadian Clock, DNA Repair, and Immune Gene Expression by Heme Oxygenase in the Retina of Drosophila

Damulewicz, Milena; Świątek, Michał; Łoboda, Agnieszka; Dulak, Józef; Bilska, Bernadetta; Przewłocki, Ryszard; Pyza, Elżbieta

doi:10.3390/genes10010006

Cited by 17 publications

(19 citation statements)

References 44 publications

(77 reference statements)

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“…The peak of ho expression at the beginning of the day in the retina protects photoreceptors from DNA damage caused by UV and white light [ 27 , 33 ], whereas the second peak at night controls expression of the immune response genes. The circadian cycling of ho mRNA also affects the expression of clock genes and other processes present in the retina, such as phototransduction, DNA repair, and autophagy [ 34 ].…”

Section: Introductionmentioning

confidence: 99%

Regulation of Heme Oxygenase and Its Cross-Talks with Apoptosis and Autophagy under Different Conditions in Drosophila

et al. 2021

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Heme oxygenase (HO) is one of the cytoprotective enzymes that can mitigate the effects of oxidative stress. Here, we found that the ho mRNA level oscillates in the brain of Drosophila melanogaster with two minima at the beginning of the day and night. This rhythm was partly masked by light as its pattern changed in constant darkness (DD). It followed a similar trend in the clock mutant per01 under light/dark regime (LD12:12); however, differences between time points were not statistically significant. In older flies (20 days old), the rhythm was vanished; however, 15 days of curcumin feeding restored this rhythm with an elevated ho mRNA level at all time points studied. In addition, flies exposed to paraquat had higher ho expression in the brain, but only at a specific time of the day which can be a protective response of the brain against stress. These findings suggest that the expression of ho in the fly’s brain is regulated by the circadian clock, light, age, exposure to stress, and the presence of exogenous antioxidants. We also found that HO cross-talks with apoptosis and autophagy under different conditions. Induction of neuronal ho was accompanied by increased transcription of apoptosis and autophagy-related genes. However, this trend changed after exposure to curcumin and paraquat. Our results suggest that HO is involved in the control of apoptotic and autophagic key processes protecting the brain against oxidative damage.

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Section: Introductionmentioning

confidence: 99%

Regulation of Heme Oxygenase and Its Cross-Talks with Apoptosis and Autophagy under Different Conditions in Drosophila

et al. 2021

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“…The circadian clock maintains daily biological rhythms by controlling the expression of target output genes, and is highly conserved between Drosophila and humans (39). Although the eye is not required for circadian behavior in flies (61,62), many genes are rhythmically expressed in the retina including most of the phototransduction machinery (49,63,64). Here, we report that retina-specific disruption of the circadian clock in Drosophila leads to progressive lightdependent retinal degeneration.…”

Section: Discussionmentioning

confidence: 83%

The Clock:cycle complex is a major transcriptional regulator ofDrosophilaphotoreceptors that protects the eye from retinal degeneration and oxidative stress

Jauregui-Lozano

Hall

Stanhope

et al. 2021

Preprint

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The aging eye experiences physiological changes that include decreased visual function and increased risk of retinal degeneration. Although there are transcriptomic signatures in the aging retina that correlate with these physiological changes, the gene regulatory mechanisms that contribute to cellular homeostasis during aging remain to be determined. Here, we integrated ATACseq and RNAseq data to identify 61 transcription factors that showed differential activity in aging Drosophila photoreceptors. These 61 age-regulated transcription factors include two circadian regulators, Clock and cycle, that showed sustained increased activity during aging. When we disrupted Clock activity in adult photoreceptors, we observed changes in expression of 15 to 20% of genes including key components of the phototransduction machinery and many eye-specific transcription factors. Using ATAC-seq, we showed that loss of Clock activity leads to changes in activity of 31 transcription factors and causes a progressive decrease in global levels of chromatin accessibility in photoreceptors. Supporting a key role for Clock-dependent transcription in the eye, disruption of Clock activity in photoreceptors also induced light-dependent retinal degeneration and increased oxidative stress, independent of light exposure. Together, our data suggests that the circadian regulators Clock and cycle act as neuroprotective factors in the aging eye by directing gene regulatory networks that maintain expression of the phototransduction machinery and counteract oxidative stress.

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“…One study revealed that KO mice showed sleep/wake disturbances compared to WT mice and that the autophagy marker LC3-II was decreased in both the olfactory bulbs and hippocampi, suggesting an early onset of autophagy dysregulation in Fus1 KO mice 93 . Heme oxygenase (Ho), whose silencing results in the downregulation of autophagy-related genes in both light and dark phases, is expressed in a circadian manner 94 . FoxOs are tightly controlled by fasting/feeding cycles and can upregulate the expression of ATG14 74 .…”

Section: Indirect Regulation Between Autophagy and The Circadian Rhytmentioning

confidence: 99%

The circadian rhythm in intervertebral disc degeneration: an autophagy connection

Zhang

Dong

et al. 2020

Exp Mol Med

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There is one circadian clock in the central nervous system and another in the peripheral organs, and the latter is driven by an autoregulatory molecular clock composed of several core clock genes. The height, water content, osmotic pressure and mechanical characteristics of intervertebral discs (IVDs) have been demonstrated to exhibit a circadian rhythm (CR). Recently, a molecular clock has been shown to exist in IVDs, abolition of which can lead to stress in nucleus pulposus cells (NPCs), contributing to intervertebral disc degeneration (IDD). Autophagy is a fundamental cellular process in eukaryotes and is essential for individual cells or organs to respond and adapt to changing environments; it has also been demonstrated to occur in human NPCs. Increasing evidence supports the hypothesis that autophagy is associated with CR. Thus, we review the connection between CR and autophagy and the roles of these mechanisms in IDD.

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Daily Regulation of Phototransduction, Circadian Clock, DNA Repair, and Immune Gene Expression by Heme Oxygenase in the Retina of Drosophila

Cited by 17 publications

References 44 publications

Regulation of Heme Oxygenase and Its Cross-Talks with Apoptosis and Autophagy under Different Conditions in Drosophila

Regulation of Heme Oxygenase and Its Cross-Talks with Apoptosis and Autophagy under Different Conditions in Drosophila

The Clock:cycle complex is a major transcriptional regulator ofDrosophilaphotoreceptors that protects the eye from retinal degeneration and oxidative stress

The circadian rhythm in intervertebral disc degeneration: an autophagy connection

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