CATALASE
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Three recently isolated catalase-negative mutants of Hansenula polymorpha lost the ability to grow on methanol but grew in media containing glucose, ethanol or glycerol. Their incubation in a medium with methanol resulted in an accumulation of hydrogen peroxide and cell death. During growth of a catalase-negative mutant in chemostat on a mixture of methanol and glucose, neither H2O2 accumulation nor cell death were observed up to the molar ratio of 10:1 of the two substrates. Cytochrome-c peroxidase and NADH-peroxidase activities were detected in the cells. In methylotrophic yeasts, catalase seems to be an enzyme characteristic of the metabolism of methanol but not needed for the metabolism of multicarbon substrates. The hydrogen peroxide produced during growth of the mutants on mixed substrates is detoxified by cytochrome-c peroxidase and other peroxidases.
Here we report that trypanosomatid flagellates of the genus Blastocrithidia possess catalase. This enzyme is not phylogenetically related to the previously characterized catalases in other monoxenous trypanosomatids, suggesting that their genes have been acquired independently. Surprisingly, Blastocrithidia catalase is less enzymatically active, compared to its counterpart from Leptomonas pyrrhocoris, posing an intriguing biological question why this gene has been retained in the evolution of trypanosomatids.
- MeSH
- fylogeneze MeSH
- katalasa chemie genetika metabolismus MeSH
- molekulární evoluce MeSH
- peroxid vodíku chemie metabolismus MeSH
- protozoální proteiny chemie genetika metabolismus MeSH
- sekvence aminokyselin MeSH
- sekvenční seřazení MeSH
- Trypanosomatina klasifikace enzymologie genetika metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- dospělí MeSH
- erytrocyty enzymologie MeSH
- ischemie mozku enzymologie krev MeSH
- katalasa patofyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mozková hypoxie MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- srovnávací studie MeSH
Catalase is an antioxidant enzyme the activity of which is crucial for the protection against damage caused by reactive oxygen species. The -262C>T polymorphism in the promoter region of catalase gene was found to be associated with altered catalase levels. In this study, peripheral blood mononuclear cells catalase activity was measured after H(2)O(2)-induced oxidative stress. C/T and T/T genotypes were associated with the decrease of catalase levels in contrast to C/C donors who had elevated catalase activity in the presence of 0.4 and 0.7 mM H(2)O(2). Genotype-dependent response of catalase activity to oxidative stress might be related to the predisposition of catalase mutant allele carriers to disorders mediated by oxidative stress.
- MeSH
- alely MeSH
- dospělí MeSH
- genotyp MeSH
- jednonukleotidový polymorfismus * MeSH
- katalasa genetika metabolismus MeSH
- leukocyty mononukleární metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mutace MeSH
- oxidační stres * MeSH
- reaktivní formy kyslíku metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Catalase is a widespread heme-containing enzyme, which converts hydrogen peroxide (H2 O2 ) to water and molecular oxygen, thereby protecting cells from the toxic effects of H2 O2 . Trypanosoma brucei is an aerobic protist, which conspicuously lacks this potent enzyme, present in virtually all organisms exposed to oxidative stress. To uncover the reasons for its absence in T. brucei, we overexpressed different catalases in procyclic and bloodstream stages of the parasite. The heterologous enzymes originated from the related insect-confined trypanosomatid Crithidia fasciculata and the human. While the trypanosomatid enzyme (cCAT) operates at low temperatures, its human homolog (hCAT) is adapted to the warm-blooded environment. Despite the presence of peroxisomal targeting signal in hCAT, both human and C. fasciculata catalases localized to the cytosol of T. brucei. Even though cCAT was efficiently expressed in both life cycle stages, the enzyme was active in the procyclic stage, increasing cell's resistance to the H2 O2 stress, yet its activity was suppressed in the cultured bloodstream stage. Surprisingly, following the expression of hCAT, the ability to establish the T. brucei infection in the tsetse fly midgut was compromised. In the mouse model, hCAT attenuated parasitemia and, consequently, increased the host's survival. Hence, we suggest that the activity of catalase in T. brucei is beneficial in vitro, yet it becomes detrimental for parasite's proliferation in both invertebrate and vertebrate hosts, leading to an inability to carry this, otherwise omnipresent, enzyme.
- MeSH
- hmyz účinky léků růst a vývoj metabolismus MeSH
- katalasa metabolismus MeSH
- peroxid vodíku farmakologie MeSH
- Trypanosoma brucei brucei účinky léků metabolismus MeSH
- Trypanosoma účinky léků metabolismus MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Catalase is one of the most abundant enzymes on Earth. It decomposes hydrogen peroxide, thus protecting cells from dangerous reactive oxygen species. The catalase-encoding gene is conspicuously absent from the genome of most representatives of the family Trypanosomatidae. Here, we expressed this protein from the Leishmania mexicana Β-TUBULIN locus using a novel bicistronic expression system, which relies on the 2A peptide of Teschovirus A. We demonstrated that catalase-expressing parasites are severely compromised in their ability to develop in insects, to be transmitted and to infect mice, and to cause clinical manifestation in their mammalian host. Taken together, our data support the hypothesis that the presence of catalase is not compatible with the dixenous life cycle of Leishmania, resulting in loss of this gene from the genome during the evolution of these parasites.
- MeSH
- faktory virulence genetika metabolismus MeSH
- katalasa genetika metabolismus MeSH
- kultivované buňky MeSH
- Leishmania mexicana genetika růst a vývoj patogenita MeSH
- myši inbrední BALB C MeSH
- myši MeSH
- protozoální proteiny genetika MeSH
- Psychodidae parazitologie MeSH
- stadia vývoje genetika MeSH
- Teschovirus genetika MeSH
- virulence MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
