Adaptations against heme toxicity in blood-feeding arthropods

Graça-Souza, Aurélio V.; Maya‐Monteiro, Clarissa M.; Paiva-Silva, Gabriela O.; Braz, Glória R.C.; Paes, Márcia Cristina; Sorgine, Marcos Henrique Ferreira; Oliveira, Marcus F.; Oliveira, Pedro L.

doi:10.1016/j.ibmb.2006.01.009

Cited by 321 publications

(303 citation statements)

References 131 publications

(137 reference statements)

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“…Beyond its utility as a sink for excess nitrogen, uric acid has been shown to have an active role in protecting against oxidative damage (33)(34)(35)(36). Overall, our results demonstrate that the RNAi-mediated silencing of ALAT activity in mosquitoes triggers strong and rapid metabolic adaptations.…”

Section: Discussionmentioning

confidence: 67%

“…Fat body, thorax, Malpighian tubules, ovary, and midgut were dissected in 1X PBS from wild-type sugar-fed (SF) and blood-fed female mosquitoes at 3,6,12,18,24,30,36, and 48 h after blood feeding. Tissues were homogenized in 13 lysis buffer (13 PBS, 1.0% Triton X-100, 12 mM sodium deoxycholate, and 2% SDS), and the protein extracts were subjected to 12% SDS-PAGE separation and Western blot analysis as previously described (10).…”

Section: Protein Extraction and Western Blotting Proceduresmentioning

confidence: 99%

“…Next, we collected excreta at several time points during blood meal digestion (6,12,18,24,36, and 48 h after blood feeding) and measured the concentration of uric acid. We also measured the heme concentration from the same excreta, because the amount of heme defecated is an indication of the progress of blood meal digestion (24,25).…”

Section: Knockdown Of Alat Expression Induces Accumulation Of Uric Acmentioning

confidence: 99%

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Effective disposal of nitrogen waste in blood‐fedAedes aegyptimosquitoes requires alanine aminotransferase

Mazzalupo¹,

Isoe²,

Belloni

et al. 2015

FASEB j.

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To better understand the mechanisms responsible for the success of female mosquitoes in their disposal of excess nitrogen, we investigated the role of alanine aminotransferase (ALAT) in blood-fed Aedes aegypti. Transcript and protein levels from the 2 ALAT genes were analyzed in sucrose-and blood-fed A. aegypti tissues. ALAT1 and ALAT2 exhibit distinct expression patterns in tissues during the first gonotrophic cycle. Injection of female mosquitoes with either double-stranded RNA (dsRNA)-ALAT1 or dsRNA ALAT2 significantly decreased mRNA and protein levels of ALAT1 or ALAT2 in fat body, thorax, and Malpighian tubules compared with dsRNA firefly luciferase-injected control mosquitoes. The silencing of either A. aegypti ALAT1 or ALAT2 caused unexpected phenotypes such as a delay in blood digestion, a massive accumulation of uric acid in the midgut posterior region, and a significant decrease of nitrogen waste excretion during the first 48 h after blood feeding. Concurrently, the expression of genes encoding xanthine dehydrogenase and ammonia transporter (Rhesus 50 glycoprotein) were significantly increased in tissues of both ALAT1-and ALAT2-deficient females. Moreover, perturbation of ALAT1 and ALAT2 in the female mosquitoes delayed oviposition and reduced egg production. These novel findings underscore the efficient mechanisms that blood-fed mosquitoes use to avoid ammonia toxicity and free radical damage.-Mazzalupo, S., Isoe, J., Belloni, V., Scaraffia, P. Y. Effective disposal of nitrogen waste in blood-fed Aedes aegypti mosquitoes requires alanine aminotransferase. FASEB J. 30, 111-120 (2016). www.fasebj.org

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Section: Discussionmentioning

confidence: 67%

Section: Protein Extraction and Western Blotting Proceduresmentioning

confidence: 99%

Section: Knockdown Of Alat Expression Induces Accumulation Of Uric Acmentioning

confidence: 99%

See 1 more Smart Citation

Effective disposal of nitrogen waste in blood‐fedAedes aegyptimosquitoes requires alanine aminotransferase

Mazzalupo¹,

Isoe²,

Belloni

et al. 2015

FASEB j.

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“…Ischemia-reperfusion injury will also bring about significant intravascular hemolysis (31,32), again supplying substrate for HO. In these cases, the detoxifying effects of heme oxygenase include the clearance of heme, which in itself is cytotoxic (33)(34)(35). In contrast, it has been shown that heme oxygenase overexpression or induction can confer cytoprotection in the absence of aberrant, extracorpuscular hemoproteins (5, 13, 36 -38).…”

Section: Discussionmentioning

confidence: 99%

Non-heme Induction of Heme Oxygenase-1 Does Not Alter Cellular Iron Metabolism

Sheftel

Kim

Ponka

2007

Journal of Biological Chemistry

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The catabolism of heme is carried out by members of the heme oxygenase (HO) family. The products of heme catabolism by HO-1 are ferrous iron, biliverdin (subsequently converted to bilirubin), and carbon monoxide. In addition to its function in the recycling of hemoglobin iron, this microsomal enzyme has been shown to protect cells in various stress models. Implicit in the reports of HO-1 cytoprotection to date are its effects on the cellular handling of heme/iron. However, the limited amount of uncommitted heme in non-erythroid cells brings to question the source of substrate for this enzyme in non-hemolytic circumstances. In the present study, HO-1 was induced by either sodium arsenite (reactive oxygen species producer) or hemin or overexpressed in the murine macrophage-like cell line, RAW 264.7. Both of the inducers elicited an increase in active HO-1; however, only hemin exposure caused an increase in the synthesis rate of the iron storage protein, ferritin. This effect of hemin was the direct result of the liberation of iron from heme by HO. Cells stably overexpressing HO-1, although protected from oxidative stress, did not display elevated basal ferritin synthesis. However, these cells did exhibit an increase in ferritin synthesis, compared with untransfected controls, in response to hemin treatment, suggesting that heme levels, and not HO-1, limit cellular heme catabolism. Our results suggest that the protection of cells from oxidative insult afforded by HO-1 is not due to the catabolism of significant amounts of cellular heme as thought previously.In the average adult, at equilibrium ϳ2 million red blood cells are being turned over every second. In a day, this process requires about 25 mg of iron (Fe) to be recycled from the hemoglobin of effete erythrocytes. Heme oxygenase 1 (HO-1) 2 is the enzyme responsible for catabolizing the heme from senescent red blood cells to release Fe, as well as equimolar amounts of carbon monoxide (CO) and biliverdin, for its eventual reuse in erythropoiesis. Another noninducible isoform of heme oxygenase with heme catabolic properties similar to HO-1, HO-2 is present in substantial levels primarily in the central nervous system and testes (1, 2). Although the heme-degrading function of HO has been known since the 1960s (3, 4), only recently has it been shown that heme oxygenases may be involved in cytoprotection against cellular stresses (for review see Camara and Soares (5), Abraham and Kappas (6), Otterbein et al. (7), and Ryter et al. (8)). This newer discovery of the potential of these enzymes as a tissue defense mechanism has spawned a flurry of studies by numerous groups who have shown by several different approaches that induction or overexpression of heme oxygenase 1 can protect tissues from various insults, including oxidative stress and immune system attack.The precise mechanism by which HO-1 mediates its protective function remains controversial. Breakdown of heme being the only known reaction catalyzed by the enzyme, extensive research has alleged that one or mo...

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“…Furthermore, lipid hydroperoxides may be formed during lipid peroxidation, which is initiated by another source of reactive species, such as O 2 -formed either by NADPH oxidase or during mitochondrial respiration. This fact suggests that the pro-oxidant action of heme can be best described as an amplification of previously formed reactive species and depends on the occurrence and magnitude of other sources of free radicals [56]. In conclusion, despite the presence of the antioxidant enzyme system described above, lipid peroxidation may occur as a result of high levels of free heme and production of radical species from other sources.…”

Section: Introductionmentioning

confidence: 92%

Cell Signaling During Trypanosoma cruzi Development in Triatominae

Silva-Neto¹

2010

TOPARAJ

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Abstract:The year 2009 is the centennial anniversary of the original description of Chagas disease by Carlos Chagas. During the last 100 years, several advances have occurred regarding our knowledge of the development of Trypanosoma cruzi and its travel along the gut of Triatominae vectors. We have also witnessed the completion of both the human and parasite genome projects; the genome of one of Chagas disease vectors, Rhodnius prolixus, is currently being sequenced. The development of T. cruzi in triatomine gut relies on several biochemical and molecular processes. The biochemistry of blood digestion and the molecular and biological aspects of parasite development are well known. However, several signaling molecules are generated during blood digestion, and their effects on parasite biology are only beginning to be understood. Here, we will summarize our current knowledge in this area with an emphasis on heme and bioactive lipids. In addition, we will highlight some recently described members of the parasite signaling machinery, which were identified through high-throughput studies, but whose ligands are unknown thus far. Finally, we will discuss some potential aspects for future investigation in this area that may strengthen our view of such a concomitant biological process in the next years.

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Adaptations against heme toxicity in blood-feeding arthropods

Cited by 321 publications

References 131 publications

Effective disposal of nitrogen waste in blood‐fedAedes aegyptimosquitoes requires alanine aminotransferase

Effective disposal of nitrogen waste in blood‐fedAedes aegyptimosquitoes requires alanine aminotransferase

Non-heme Induction of Heme Oxygenase-1 Does Not Alter Cellular Iron Metabolism

Cell Signaling During Trypanosoma cruzi Development in Triatominae

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