On the physico-chemical and physiological requirements of hemozoin formation promoted by perimicrovillar membranes in Rhodnius prolixus midgut

Stiebler, Renata; Timm, Bruno Lisboa; Oliveira, Pedro L.; Hearne, G. R.; Egan, Timothy J.; Oliveira, Marcus F.

doi:10.1016/j.ibmb.2009.12.013

Cited by 26 publications

(43 citation statements)

References 61 publications

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“…However, the apparent IC50 for inhibition of hemozoin formation induced by perimicrovillar membranes found here (w1 mM) is more than 10-fold lower than the 75 mM Ki reported for the Plasmodium extract, making it an inhibitor as efficient as chloroquine in this system, which showed an IC50 of about 30 mM (Oliveira et al, 2000b). Both in Plasmodium and Rhodnius, hemozoin formation seems to involve participation of specific proteins that trigger formation of nucleation sites for heme aggregation at hydrophilic/ hydrophobic (lipid) interface (Mury et al, 2009;Stiebler et al, 2010). The differences observed in sensitivity towards SnPP-IX could be explained by the differences in proteins involved in this step in each organism, the Heme Detoxification Protein (HDP) in Plasmodium (Jani et al, 2008) and the perimicrovillar membrane a-glucosidase in Rhodnius (Mury et al, 2009).…”

Section: Discussioncontrasting

confidence: 50%

Sn-protoporphyrin inhibits both heme degradation and hemozoin formation in Rhodnius prolixus midgut

Caiaffa

Stiebler

Oliveira

et al. 2010

Insect Biochemistry and Molecular Biology

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Section: Discussioncontrasting

confidence: 50%

Sn-protoporphyrin inhibits both heme degradation and hemozoin formation in Rhodnius prolixus midgut

Caiaffa

Stiebler

Oliveira

et al. 2010

Insect Biochemistry and Molecular Biology

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“…Several important issues must be considered in this context: i ) the total heme levels in the vector midgut reach millimolar concentrations; of note, heme crystallisation into hemozoin (Hz) is a very efficient heme detoxification process that takes place in the midgut of different triatomine species [55], [56]. Interestingly, recent evidence has demonstrated that Hz represents by far the dominant iron-containing compound found in the triatomine midgut, comprising at least 97% of whole iron species [57]. Therefore, despite the very low “ free ” heme levels in the R. prolixus midgut [57], it is conceivable that small amounts of heme would be physiologically relevant to allow progression of the T. cruzi life cycle in this compartment.…”

Section: Discussionmentioning

confidence: 99%

Heme-Induced ROS in Trypanosoma Cruzi Activates CaMKII-Like That Triggers Epimastigote Proliferation. One Helpful Effect of ROS

et al. 2011

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Heme is a ubiquitous molecule that has a number of physiological roles. The toxic effects of this molecule have been demonstrated in various models, based on both its pro-oxidant nature and through a detergent mechanism. It is estimated that about 10 mM of heme is released during blood digestion in the blood-sucking bug's midgut. The parasite Trypanosoma cruzi, the agent of Chagas' disease, proliferates in the midgut of the insect vector; however, heme metabolism in trypanosomatids remains to be elucidated. Here we provide a mechanistic explanation for the proliferative effects of heme on trypanosomatids. Heme, but not other porphyrins, induced T. cruzi proliferation, and this phenomenon was accompanied by a marked increase in reactive oxygen species (ROS) formation in epimastigotes when monitored by ROS-sensitive fluorescent probes. Heme-induced ROS production was time-and concentration-dependent. In addition, lipid peroxidation and the formation of 4-hydroxy-2-nonenal (4-HNE) adducts with parasite proteins were increased in epimastigotes in the presence of heme. Conversely, the antioxidants urate and GSH reversed the heme-induced ROS. Urate also decreased parasite proliferation. Among several protein kinase inhibitors tested only specific inhibitors of CaMKII, KN93 and Myr-AIP, were able to abolish heme-induced ROS formation in epimastigotes leading to parasite growth impairment. Taken together, these data provide new insight into T. cruzi- insect vector interactions: heme, a molecule from the blood digestion, triggers epimastigote proliferation through a redox-sensitive signalling mechanism.

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“…Rhodnius prolixus is a classical model for the study of oxidative stress associated with blood ingestion (Graça-Souza et al, 2006;Caiaffa et al, 2010;Stiebler et al, 2010). For this reason, we used this species to analyze the response of mutants and wild-type bugs to the exposure of photo and heme oxidative stress.…”

Section: Experimental Animalsmentioning

confidence: 99%

Oxidative stress, photodamage and the role of screening pigments in insect eyes

Insausti¹,

Gall²,

Lazzari

2013

Journal of Experimental Biology

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SUMMARYUsing red-eyed mutant triatomine bugs (Hemiptera: Reduvidae), we tested the hypothesis of an alternative function of insect screening pigments against oxidative stress. To test our hypothesis, we studied the morphological and physiological changes associated with the mutation. We found that wild-type eyes possess a great amount of brown and red screening pigment inside the primary and secondary pigment cells as well as in the retinular cells. Red-eyed mutants, however, have only scarce red granules inside the pigmentary cells. We then compared the visual sensitivity of red-eyed mutants and wild types by measuring the photonegative responses of insects reared in light:dark cycles [12h:12h light:dark (LD)] or constant darkness (DD). Finally, we analyzed both the impact of oxidative stress associated with blood ingestion and photodamage of UV light on the eye retina. We found that red-eyed mutants reared in DD conditions were the most sensitive to the light intensities tested. Retinae of LDreared mutants were gradually damaged over the life cycle, while for DD-reared insects retinae were conserved intact. No retinal damage was observed in non-fed mutants exposed to UV light for 2weeks, whereas insects fed on blood prior to UV exposure showed clear signs of retinal damage. Wild-type insects exposed to UV light showed a marked increase in the amount and density of screening pigments.

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On the physico-chemical and physiological requirements of hemozoin formation promoted by perimicrovillar membranes in Rhodnius prolixus midgut

Cited by 26 publications

References 61 publications

Sn-protoporphyrin inhibits both heme degradation and hemozoin formation in Rhodnius prolixus midgut

Sn-protoporphyrin inhibits both heme degradation and hemozoin formation in Rhodnius prolixus midgut

Heme-Induced ROS in Trypanosoma Cruzi Activates CaMKII-Like That Triggers Epimastigote Proliferation. One Helpful Effect of ROS

Oxidative stress, photodamage and the role of screening pigments in insect eyes

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