Genetic and biochemical analysis of glutathione-<i>S</i>-transferase in the oxygen defense system of <i>Drosophila melanogaster</i>

Parkes, Tony L.; Hilliker, Arthur J.; Phillips, J. P.

doi:10.1139/g93-134

Cited by 69 publications

(40 citation statements)

References 40 publications

(47 reference statements)

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“…Consistent with this scenario, we observed decreased JNK signaling and increased GST activity in the flies with Dpt overexpression and confirmed these changes by real-time PCR and enzyme activity assays, respectively. GST has been shown to play a role in antioxidant defense and has glutathione reductase activity in Drosophila (20,22,54). In particular, GstD3, which was up-regulated in the flies with Dpt overexpression, has also been shown to respond to dietary H 2 O 2 , and both GstD3 and GstE1 can metabolize 4-hydroxynonenal, a highly toxic aldehyde produced by lipid peroxidation in cells in response to oxidative stress (54,55).…”

Section: Discussionmentioning

confidence: 99%

“…Under conditions of oxidative stress, GSTs have glutathione peroxidase activity and protect against electrophiles and oxidative stress by altering cellular glutathione levels (21). Because of a lack of functional glutathione peroxidase enzymes in Drosophila, flies rely instead on the activity of the more general detoxification enzymes, GSTs, to carry out a peroxidase function (22,23). The up-regulation of genes encoding these antioxidant enzymes (i.e.…”

Section: Overexpression Of Diptericin Increases Hyperoxia Tolerance-mentioning

confidence: 99%

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Antimicrobial Peptides Increase Tolerance to Oxidant Stress in Drosophila melanogaster

Zhao¹,

Zhou²,

Haddad

2011

Journal of Biological Chemistry

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It is well appreciated that reactive oxygen species (ROS) are deleterious to mammals, including humans, especially when generated in abnormally large quantities from cellular metabolism. Whereas the mechanisms leading to the production of ROS are rather well delineated, the mechanisms underlying tissue susceptibility or tolerance to oxidant stress remain elusive. Through an experimental selection over many generations, we have previously generated Drosophila melanogaster flies that tolerate tremendous oxidant stress and have shown that the family of antimicrobial peptides (AMPs) is over-represented in these tolerant flies. Furthermore, we have also demonstrated that overexpression of even one AMP at a time (e.g. Diptericin) allows wild-type flies to survive much better in hyperoxia. In this study, we used a number of experimental approaches to investigate the potential mechanisms underlying hyperoxia tolerance in flies with AMP overexpression. We demonstrate that flies with Diptericin overexpression resist oxidative stress by increasing antioxidant enzyme activities and preventing an increase in ROS levels after hyperoxia. Depleting the GSH pool using buthionine sulfoximine limits fly survival, thus confirming that enhanced survival observed in these flies is related to improved redox homeostasis. We conclude that 1) AMPs play an important role in tolerance to oxidant stress, 2) overexpression of Diptericin changes the cellular redox balance between oxidant and antioxidant, and 3) this change in redox balance plays an important role in survival in hyperoxia.Oxygen is essential for aerobic life. However, except for the beneficial role in wound healing, too little or too much oxygen can induce morbidity and mortality (1, 2). Mammalian aging and numerous diseases such as neurodegenerative diseases and chronic inflammatory diseases, as well as injury to the heart, lungs, retina, brain, and other organs due to ischemia and reperfusion states, result, by and large, from oxidant injury (3-6). High O 2 -induced oxidant injury could occur in cells in every organ, especially in the lungs, retina, heart, and brain (7,8). Prolonged exposure to high O 2 generates excessive reactive oxygen species (ROS), 2 induces cell death and oxidative stress responses, affects the immune response and DNA integrity, and modulates cell growth (5, 9 -11).Drosophila melanogaster has similar O 2 response pathways as mammals, and research on flies has enhanced our understanding of oxidant stress (12)(13)(14). In the past, through an experimental selection design over many generations, we have successfully generated D. melanogaster flies that tolerate tremendously high O 2 -induced oxidative stress. Microarray analysis has revealed that the family of antimicrobial peptides (AMPs) is over-represented among the up-regulated genes in these tolerant flies. We have further demonstrated that overexpression of even one AMP gene at a time (e.g. Diptericin (Dpt)) allows wild-type flies to survive much better in hyperoxia (15). To our knowledge, this is t...

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Section: Discussionmentioning

confidence: 99%

Section: Overexpression Of Diptericin Increases Hyperoxia Tolerance-mentioning

confidence: 99%

Antimicrobial Peptides Increase Tolerance to Oxidant Stress in Drosophila melanogaster

Zhao¹,

Zhou²,

Haddad

2011

Journal of Biological Chemistry

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“…These include the mosquito homologue of 1-cys peroxiredoxin, which has been implicated in protecting cells from oxygen radicals formed as a product of aerobic metabolism (29), and glutathione S-transferase (30).…”

Section: Discussionmentioning

confidence: 99%

Analysis of the Plasmodium and Anopheles Transcriptional Repertoire during Ookinete Development and Midgut Invasion

Abraham

Islam

Srinivasan

et al. 2004

Journal of Biological Chemistry

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Plasmodium, the causative agent of malaria, has to undergo sexual differentiation and development in anopheline mosquitoes for transmission to occur. To isolate genes specifically induced in both organisms during the early stages of Plasmodium differentiation in the mosquito, two cDNA libraries were constructed, one enriched for sequences expressed in differentiating Plasmodium berghei ookinetes and another enriched for sequences expressed in Anopheles stephensi guts containing invading ookinetes and early oocysts. Sequencing of 457 ookinete library clones and 652 early oocyst clones represented 175 and 346 unique expressed sequence tags, respectively. Nine of 13 Plasmodium and four of the five Anopheles novel expressed sequence tags analyzed on Northern blots were induced during ookinete differentiation and mosquito gut invasion. Ancaspase-7, an Anopheles effector caspase, is proteolytically activated during Plasmodium invasion of the midgut. WARP, a gene encoding a Plasmodium surface protein with a von Willebrand factor A-like adhesive domain, is expressed only in ookinetes and early oocysts. An anti-WARP polyclonal antibody strongly inhibits (70 -92%) Plasmodium development in the mosquito, making it a candidate antigen for transmission blocking vaccines. The present results and those of an accompanying report

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“…Extensive genetic analysis of SOD1 has revealed the critical role of this enzyme in many diverse aspects of the biology of Drosophila. SOD1-null mutants of Drosophila, in sharp contrast to those of mice (10), are debilitated severely and exhibit male sterility and reduced female fertility, hypersensitivity to paraquat, ionizing radiation, transition metals, hyperoxia (5), and buthionine sulfoximine-mediated depletion of glutathione (11), retinal degeneration (12), premature aging (13), and reduction of adult life span by 85-90% (5). All these phenotypes can be restored virtually to WT by genomic Sod1 transgenes (14).…”

mentioning

confidence: 99%

RNA interference-mediated silencing of Sod2 in Drosophila leads to early adult-onset mortality and elevated endogenous oxidative stress

Kirby

Hilliker

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

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197

135

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Oxidative stress has been widely implicated as an important factor in the aging process. Because mitochondrial respiration is the principal source of reactive oxygen within cells, the mitochondrially localized superoxide dismutase (SOD) 2 is thought to play an important front-line defensive role against aging-related oxidative stress. Although genetic studies with mutants deficient in SOD1, the predominantly cytosolic isoform of SOD, have been instrumental in elucidating the role of reactive oxygen metabolism in aging in Drosophila, the lack of available mutations in the Sod2 gene has hampered an equivalent analysis of the participation of this important antioxidant enzyme in the Drosophila aging model. Here we report that ablation of mitochondrial SOD2 through expression of a GAL4-regulated, inverted-repeat Sod2 RNA-interference transgene in an otherwise normal animal causes increased endogenous oxidative stress, resulting in loss of essential enzymatic components of the mitochondrial respiratory chain and the tricarboxylic acid cycle, enhances sensitivity to applied oxidative stress, and causes early-onset mortality in young adults. In sharp contrast, ablation of SOD2 has no overt effect on the development of larvae and pupae, which may reflect a fundamental transition in oxygen utilization and͞or reactive oxygen metabolism that occurs during metamorphosis from larval to adult life.

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Genetic and biochemical analysis of glutathione-S-transferase in the oxygen defense system of Drosophila melanogaster

Cited by 69 publications

References 40 publications

Antimicrobial Peptides Increase Tolerance to Oxidant Stress in Drosophila melanogaster

Antimicrobial Peptides Increase Tolerance to Oxidant Stress in Drosophila melanogaster

Analysis of the Plasmodium and Anopheles Transcriptional Repertoire during Ookinete Development and Midgut Invasion

RNA interference-mediated silencing of Sod2 in Drosophila leads to early adult-onset mortality and elevated endogenous oxidative stress

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