Specificity and kinetics of a mitochondrial peroxiredoxin of Leishmania infantum

Castro, Helena Carla; Budde, Heike; Flohé, Leopold; Hofmann, Birgit; Lünsdorf, Heinrich; Wissing, Joseph; Toms, Ana M

doi:10.1016/s0891-5849(02)01088-2

Cited by 56 publications

(40 citation statements)

References 44 publications

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“…In situ detection of DNA fragments by terminal deoxynucleotidyltransferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL) was performed with an in situ cell death detection kit, TMR red (Roche), according to the manufacturer's instructions. Briefly, 10 7 promastigotes harvested at early log phase and transfected with either LdmPrx/pX63pol or pX63pol or untransfected cells from the early (2 ϫ 10 6 ) and late (6 ϫ 10 7 ) logarithmic phase in 1 ml of M199 medium were exposed to 1 to 3 mM H 2 O 2 for 3 h. Control cells were incubated in PBS. Cells were used to coat poly-L-lysinecovered slides and fixed with 4% paraformaldehyde.…”

Section: Methodsmentioning

confidence: 99%

“…Peroxiredoxins localized in the cytosol appear to be ideal to protect the parasite against oxidative attack from the outside. Peroxiredoxins localized in the mitochondrion seem to be of particular interest, since kinetoplastids are known to generate H 2 O 2 as a byproduct of their own mitochondrial energy metabolism (51).For the mitochondrial peroxiredoxin of L. infantum (LimTXNPx), as well as for the cytoplasmic peroxiredoxins from L. infantum (LicTXNPx), L. chagasi (LcPxn1, LcPxn2) and L. donovani (LdH6TXNPx), it was shown that they all can detoxify ROS, with a preference for H 2 O 2 and tert-butyl hydroperoxide (t-BOOH) (6,10,11,21). It was further shown that overexpression of LcPxn1 in L. chagasi enhanced survival when exposed to different ROS and RNS and also enhanced survival within U937 macrophage cells (6).…”

mentioning

confidence: 99%

“…For the mitochondrial peroxiredoxin of L. infantum (LimTXNPx), as well as for the cytoplasmic peroxiredoxins from L. infantum (LicTXNPx), L. chagasi (LcPxn1, LcPxn2) and L. donovani (LdH6TXNPx), it was shown that they all can detoxify ROS, with a preference for H 2 O 2 and tert-butyl hydroperoxide (t-BOOH) (6,10,11,21). It was further shown that overexpression of LcPxn1 in L. chagasi enhanced survival when exposed to different ROS and RNS and also enhanced survival within U937 macrophage cells (6).…”

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confidence: 99%

“…Peroxiredoxins are found in a great variety of organisms, where they fulfill distinct functions, such as detoxification, signaling, or differentiation (25). In different members of the family Trypanosomatidae, cytosolic, as well as mitochondrial, peroxiredoxins were found (6,10,11,21). Peroxiredoxins localized in the cytosol appear to be ideal to protect the parasite against oxidative attack from the outside.…”

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Expression of a Mitochondrial Peroxiredoxin Prevents Programmed Cell Death inLeishmania donovani

Harder

Bente

Isermann³

et al. 2006

Eukaryot Cell

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Leishmania promastigote cells transmitted by the insect vector get phagocytosed by macrophages and convert into the amastigote form. During development and transformation, the parasites are exposed to various concentrations of reactive oxygen species, which can induce programmed cell death (PCD). We show that a mitochondrial peroxiredoxin (LdmPrx) protects Leishmania donovani from PCD. Whereas this peroxiredoxin is restricted to the kinetoplast area in promastigotes, it covers the entire mitochondrion in amastigotes, accompanied by dramatically increased expression. A similar change in the expression pattern was observed during the growth of Leishmania from the early to the late logarithmic phase. Recombinant LdmPrx shows typical peroxiredoxin-like enzyme activity. It is able to detoxify organic and inorganic peroxides and prevents DNA from hydroxyl radical-induced damage. Most notably, Leishmania parasites overexpressing this peroxiredoxin are protected from hydrogen peroxide-induced PCD. This protection is also seen in promastigotes grown to the late logarithmic phase, also characterized by high expression of this peroxiredoxin. Apparently, the physiological role of this peroxiredoxin is stabilization of the mitochondrial membrane potential and, as a consequence, inhibition of PCD through removal of peroxides.Leishmania parasites affect more than 12 million people worldwide, with an estimated 2 million new cases each year (WHO World Health Report, 2004, http://www.who.int/whr /en). Depending on the species involved, symptoms range from the self-healing cutaneous form (Leishmania major) to the fatal visceral form (L. donovani). The parasite is transmitted as the infective promastigote form from the gut of its insect vector, female phlebotomine flies of the genera Phlebotomus and Lutzomyia, to mammalian hosts. Promastigotes get phagocytosed by macrophages and convert into the amastigote form, which is able to survive and replicate within phagolysosomes. During phagocytosis of Leishmania promastigotes, the macrophages produce different reactive oxygen species (ROS) to kill the parasites. ROS readily react with proteins, DNA, and lipids and have been implicated in a wide variety of cell functions, such as signal transduction, redox homeostasis, apoptosis, aging, tumor progression, and pathogen infection (9,19,42,58). Numerous reports have shown that Leishmania parasites are susceptible to ROS-and RNS (reactive nitrogen species)-mediated toxicity (41, 57). In order to survive and establish an infection, they have to cope with these pro-oxidants. In Trypanosomatidae, it was shown that peroxiredoxins are the major antioxidant enzymes that can use different ROS and RNS like H 2 O 2 , hydroperoxides, and ONOO as substrates (56). Peroxiredoxins are found in a great variety of organisms, where they fulfill distinct functions, such as detoxification, signaling, or differentiation (25). In different members of the family Trypanosomatidae, cytosolic, as well as mitochondrial, peroxiredoxins were found (6,10,11,21). Peroxire...

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Expression of a Mitochondrial Peroxiredoxin Prevents Programmed Cell Death inLeishmania donovani

Harder

Bente

Isermann³

et al. 2006

Eukaryot Cell

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“…The decrease in rate was not attributed to the exhaustion of substrate or product inhibition by NADP + , but rather to the inactivation of TPx by peroxide. Substrate inactivation was also shown to occur in the peroxiredoxins (Prxs) from Kinetoplastida, including Leishmania major, L. donovani and Trypanosoma brucei, but not in Crithidia fasciculate (Nogoceke et al, 1997;Castro et al, 2002;Flohe et al, 2002;Budde et al, 2003). In contrast, the homologous bacterial peroxiredoxin AhpC efficiently detoxifies mM levels of hydrogen peroxide and cumene peroxide without any indication of peroxide-dependent inactivation (Niimura et al, 1995;Poole, 1996).…”

Section: The Hyperoxidation Of Peroxiredoxinsmentioning

confidence: 99%

The Peroxiredoxin Repair Proteins

Jönsson

Lowther

2007

Subcellular Biochemistry

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Sulfiredoxin and sestrin are cysteine sulfinic acid reductases that selectively reduce or repair the hyperoxidized forms of typical 2-Cys peroxiredoxins within eukaryotes. As such these enzymes play key roles in the modulation of peroxide-mediated cell signaling and cellular defense mechanisms. The unique structure of sulfiredoxin facilitates access to the peroxiredoxin active site and novel sulfur chemistry.

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Reactive Inorganic Oxy‐Species of C, N, S, and P

Sharma¹

2012

Oxidation of Amino Acids, Peptides, and Proteins

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Specificity and kinetics of a mitochondrial peroxiredoxin of Leishmania infantum

Cited by 56 publications

References 44 publications

Expression of a Mitochondrial Peroxiredoxin Prevents Programmed Cell Death inLeishmania donovani

Expression of a Mitochondrial Peroxiredoxin Prevents Programmed Cell Death inLeishmania donovani

The Peroxiredoxin Repair Proteins

Reactive Inorganic Oxy‐Species of C, N, S, and P

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