Genetic Link between Heme Oxygenase and the Signaling Pathway of DNA Damage in&lt;i&gt; Drosophila&lt;/i&gt; &lt;i&gt;Melanogaster&lt;/i&gt;

Ida, Hiroyuki; Suyari, Osamu; Shimamura, Mai; Tai, Tran Tien; Yamaguchi, Masamitsu; Taketani, Shigeru

doi:10.1620/tjem.231.117

Cited by 10 publications

(14 citation statements)

References 41 publications

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“…Ida et al ( 2013 ) also observed a significant drop in proliferating cells and an increase of DNA damage detected in the eye imaginal disks of the larva after treatment with HO dsRNA. Ida et al ( 2013 ) performed a genomic screen leading to the identification of eight genomic regions that suppressed the observed rough eye phenotype during HO knockdown. This indicates that specific genes on these isolated regions may interact with HO and help counteract its loss during a knockdown event, however further work is needed to isolate specific genes.…”

Section: Heme Catabolismmentioning

confidence: 88%

“…Immunostaining the eye tissue of HO knockdown larvae revealed high concentrations of activated caspase-3, an apoptotic marker, as well as larger than normal iron deposits, both of which were thought to contribute to the rough eye phenotype observed. This observed phenotype was later linked to G1/S arrest of the cell cycle leading to cell death due to increased generation of reactive oxygen species (Ida et al, 2013 ). Ida et al ( 2013 ) also observed a significant drop in proliferating cells and an increase of DNA damage detected in the eye imaginal disks of the larva after treatment with HO dsRNA.…”

Section: Heme Catabolismmentioning

confidence: 99%

“…This observed phenotype was later linked to G1/S arrest of the cell cycle leading to cell death due to increased generation of reactive oxygen species (Ida et al, 2013 ). Ida et al ( 2013 ) also observed a significant drop in proliferating cells and an increase of DNA damage detected in the eye imaginal disks of the larva after treatment with HO dsRNA. Ida et al ( 2013 ) performed a genomic screen leading to the identification of eight genomic regions that suppressed the observed rough eye phenotype during HO knockdown.…”

Section: Heme Catabolismmentioning

confidence: 99%

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Ironing out the Details: Exploring the Role of Iron and Heme in Blood-Sucking Arthropods

2018

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Heme and iron are essential molecules for many physiological processes and yet have the ability to cause oxidative damage such as lipid peroxidation, protein degradation, and ultimately cell death if not controlled. Blood-sucking arthropods have evolved diverse methods to protect themselves against iron/heme-related damage, as the act of bloodfeeding itself is high risk, high reward process. Protective mechanisms in medically important arthropods include the midgut peritrophic matrix in mosquitoes, heme aggregation into the crystalline structure hemozoin in kissing bugs and hemosomes in ticks. Once heme and iron pass these protective mechanisms they are presumed to enter the midgut epithelial cells via membrane-bound transporters, though relatively few iron or heme transporters have been identified in bloodsucking arthropods. Upon iron entry into midgut epithelial cells, ferritin serves as the universal storage protein and transport for dietary iron in many organisms including arthropods. In addition to its role as a nutrient, heme is also an important signaling molecule in the midgut epithelial cells for many physiological processes including vitellogenesis. This review article will summarize recent advancements in heme/iron uptake, detoxification and exportation in bloodfeeding arthropods. While initial strides have been made at ironing out the role of dietary iron and heme in arthropods, much still remains to be discovered as these molecules may serve as novel targets for the control of many arthropod pests.

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Section: Heme Catabolismmentioning

confidence: 88%

Section: Heme Catabolismmentioning

confidence: 99%

Section: Heme Catabolismmentioning

confidence: 99%

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Ironing out the Details: Exploring the Role of Iron and Heme in Blood-Sucking Arthropods

2018

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“…Although they differ in distribution and functions, they both act as cytoprotective and anti-apoptotic agents in an organism, by scavenging reactive oxygen species (ROS; reviewed in [1]). In Drosophila melanogaster , there is only one gene encoding HO [2] that plays an important role in development [3] and in controlling the signaling pathway of DNA damage [4]. Any other functions of HO in insects are still unknown.…”

Section: Introductionmentioning

confidence: 99%

Interactions Between the Circadian Clock and Heme Oxygenase in the Retina of Drosophila melanogaster

et al. 2016

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The Drosophila retina has an autonomous peripheral circadian clock in which the expression of the gene encoding heme oxygenase (HO) is under circadian control with the ho mRNA peaking at the beginning of the day and in the middle of the night. The function of HO in the retina is unknown, but we observed that it regulates the circadian clock and protects photoreceptors against DNA damage. The decline in HO level increases and decreases the expression of the canonical clock genes period (per) and Clock (Clk), respectively. The opposite result was observed after increasing HO expression. Among three products of HO activity—carbon monoxide (CO), ferrous ions, and biliverdin—the latter has no effect on per and Clk expressions, but CO exerts the same effect as the increase of ho expression. This suggests that HO action on the clock is mediated by CO, which may affect Clk expression during the day and the level of per expression. While ho expression is not stimulated by nitric oxide (NO), NO has the same effect on the clock as HO, increasing Clk expression and decreasing the expression of per.Electronic supplementary materialThe online version of this article (doi:10.1007/s12035-016-0026-9) contains supplementary material, which is available to authorized users.

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“…In mammals, two HO proteins, inducible HO-1 and constitutive HO-2, are encoded by two different genes and have cytoprotective and anti-apoptotic functions by scavenging reactive oxygen species (ROS) 1 . Drosophila has only one gene encoding HO 2 that plays an important role in development 3 and in controlling the DNA damage signalling pathway 4 .…”

Section: Introductionmentioning

confidence: 99%

Haeme oxygenase protects against UV light DNA damages in the retina in clock-dependent manner

Damulewicz

Łoboda

Józkowicz

et al. 2017

Sci Rep

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In the present study, we showed that in the retina of Drosophila, the expression of the ho gene, encoding haeme oxygenase (HO), is regulated by light but only at the beginning of the day. This timing must be set by the circadian clock as light pulses applied at other time points during the day do not increase the ho mRNA level. Moreover, light-induced activation of HO does not depend on the canonical phototransduction pathway but instead involves cryptochrome and is enhanced by ultraviolet (UV) light. Interestingly, the level of DNA damage in the retina after UV exposure was inversely related to the circadian oscillation of the ho mRNA level during the night, being the highest when the HO level was low and reversed during the day. Accordingly, induction of HO by hemin was associated with low DNA damage, while inhibition of HO activity by SnPPIX aggravated the damage. Our data suggest that HO acts in the retina to decrease oxidative DNA damage in photoreceptors caused by UV-rich light in the morning.Haeme oxygenase (HO) catalyses the degradation of haeme to carbon monoxide (CO), ferrous ions and biliverdin. In mammals, two HO proteins, inducible HO-1 and constitutive HO-2, are encoded by two different genes and have cytoprotective and anti-apoptotic functions by scavenging reactive oxygen species (ROS) 1 . Drosophila has only one gene encoding HO 2 that plays an important role in development 3 and in controlling the DNA damage signalling pathway 4 .In a previous study, we found that ho in the fly's retina is cyclically expressed with two peaks, 1 h after lights-on and 4 h after lights-off in a light/dark cycle 5 . This rhythm must be generated by a circadian clock because it is maintained in constant darkness (DD) and disrupted in the arrhythmic per 01 mutant 5 . However, HO also has an impact on the molecular mechanism of the clock 5 .The molecular mechanism of the circadian clock is based on interlocked transcriptional-translational negative and positive feedback loops. Late in the evening, the CLOCK (CLK) protein, after reaching the appropriate level, forms dimers with CYCLE (CYC) 6 , and these heterodimers are transported into the nucleus where they bind to the promoter regulatory sequence E-box of per, tim and ccg (clock-controlled gene) genes, inducing their expression. At the end of the night, the amount of these gene products is sufficient to form PERIOD (PER) and TIMELESS (TIM) heterodimers 7 , and PER/TIM complexes are transported into the nucleus, where they bind to CLK/CYC and repress their activity, thereby inhibiting the transcription of their own genes per and tim 8 . This is the main negative feedback loop of the molecular circadian clock. When per and tim transcription is inhibited, transcription of clk is activated, and the CLK protein is synthesized. Next, CLK and CYC form heterodimers involved in the second, positive feedback loop 6 . In the nucleus, these transcription factors bind to the E-box sequence of vrille (vri) and par domain protein 1 (pdp1) genes, activating their transcription 9,10...

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Genetic Link between Heme Oxygenase and the Signaling Pathway of DNA Damage in<i> Drosophila</i> <i>Melanogaster</i>

Cited by 10 publications

References 41 publications

Ironing out the Details: Exploring the Role of Iron and Heme in Blood-Sucking Arthropods

Ironing out the Details: Exploring the Role of Iron and Heme in Blood-Sucking Arthropods

Interactions Between the Circadian Clock and Heme Oxygenase in the Retina of Drosophila melanogaster

Haeme oxygenase protects against UV light DNA damages in the retina in clock-dependent manner

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