A Peroxiredoxin Specifically Expressed in Two Types of Pharyngeal Neurons is Required for Normal Growth and Egg Production in Caenorhabditis elegans

Isermann, Kerstin; Liebau, Eva; Roeder, Thomas; Bruchhaus, Iris

doi:10.1016/j.jmb.2004.03.021

Cited by 42 publications

(49 citation statements)

References 54 publications

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“…The enzymatic kinetics observed for the removal of H 2 O 2 is comparable to that of peroxiredoxins from P. falciparum, C. elegans, human neutrophils, and Pisum sativum, where similar peroxidase assays were used (Fig. 1D) (8,26,27,32).…”

Section: Resultsmentioning

confidence: 67%

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: Resultsmentioning

confidence: 67%

Expression of a Mitochondrial Peroxiredoxin Prevents Programmed Cell Death inLeishmania donovani

Harder

Bente

Isermann³

et al. 2006

Eukaryot Cell

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“…Moreover, there is no difference between the sensitivity of wild type and prdx-2 mutants to higher concentrations of hydrogen peroxide, at which PRDX-2 is hyperoxidized ( Fig. S2F) (17). Taken together, these data suggest that the thioredoxin peroxidase activity of reduced PRDX-2 plays an important role in protecting C. elegans against hydrogen peroxide.…”

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confidence: 69%

“…In addition to reduced peroxide resistance, reduced lifespan, increased expression of phase II detoxification genes, and increased arsenite resistance (Figs. 1-3 and Table S1), prdx-2 mutant animals have a reduced size and fecundity (17). Intestinal PRDX-2 did not restore normal growth or fecundity or indeed rescue any of these phenotypes, aside from peroxide sensitivity (Fig.…”

Section: Tissue-specific Functions Of Prdx-2 In Stress Resistance Andmentioning

confidence: 86%

A redox-sensitive peroxiredoxin that is important for longevity has tissue- and stress-specific roles in stress resistance

Oláhová

Taylor²,

Khazaipoul³

et al. 2008

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

140

139

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“…The plasmid pJC45 containing the His-tagged variant of C. elegans PRDX-2 was kindly provided by Dr. Bruchhaus (13) and transformed into E. coli BL21 (DE3)(pAPlacIQ). After induction with isopropyl-beta-d-thiogalactopyranoside and overexpression of PRDX-2, the protein was purified with an Ni-NTA column using standard procedures.…”

Section: Prdx-2 Purification Reduction and Overoxidationmentioning

confidence: 99%

Is Overoxidation of Peroxiredoxin Physiologically Significant?

Thamsen

Kumsta

et al. 2011

Antioxidants & Redox Signaling

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Eukaryotic peroxiredoxins are highly susceptible to sulfinic acid formation. This overoxidation, which is thought to convert peroxiredoxins into chaperones, can be reversed by sulfiredoxins. Several organisms, including Caenorhabditis elegans, lack sulfiredoxins but encode sestrins, proteins proposed to be functionally equivalent. We induced peroxiredoxin overoxidation in C. elegans with a short peroxide pulse. We found that reduction of overoxidized peroxiredoxin 2 (PRDX-2) was extremely slow and sestrin-independent, strongly implying that worms lack an efficient repair system. Analysis of PRDX-2's overoxidation status during C. elegans lifespan revealed no accumulation of overoxidized PRDX-2 at any point, questioning whether PRDX-2 overoxidation in worms is physiologically relevant. Antioxid. Redox Signal. 14, 725-730.

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A Peroxiredoxin Specifically Expressed in Two Types of Pharyngeal Neurons is Required for Normal Growth and Egg Production in Caenorhabditis elegans

Cited by 42 publications

References 54 publications

Expression of a Mitochondrial Peroxiredoxin Prevents Programmed Cell Death inLeishmania donovani

Expression of a Mitochondrial Peroxiredoxin Prevents Programmed Cell Death inLeishmania donovani

A redox-sensitive peroxiredoxin that is important for longevity has tissue- and stress-specific roles in stress resistance

Is Overoxidation of Peroxiredoxin Physiologically Significant?

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