4.6 Article

Tryparedoxin peroxidases from Trypanosoma cruzi: High efficiency in the catalytic elimination of hydrogen peroxide and peroxynitrite

Journal

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
Volume 507, Issue 2, Pages 287-295

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1016/j.abb.2010.12.014

Keywords

Trypanosoma cruzi; Tryparedoxin peroxidase; Peroxiredoxin; Peroxynitrite; Hydrogen peroxide; Peroxidase

Funding

  1. Howard Hughes Medical Institute
  2. Programa de Desarrollo Tecnologico [PDT 079]
  3. Ministerio de Educacion y Cultura

Ask authors/readers for more resources

During host cell infection, Trypanosoma cruzi parasites are exposed to reactive oxygen and nitrogen species. As part of their antioxidant defense systems, they express two tryparedoxin peroxidases (TXNPx), thiol-dependent peroxidases members of the peroxiredoxin family. In this work, we report a kinetic characterization of cytosolic (c-TXNPx) and mitochondrial (m-TXNPx) tryparedoxin peroxidases from T. cruzi. Both c-TXNPx and m-TXNPx rapidly reduced hydrogen peroxide (k = 3.0 x 10(7) and 6 x 10(6) M-1 s(-1) at pH 7.4 and 25 degrees C, respectively) and peroxynitrite (k = 1.0 x 10(6) and k = 1.8 x 10(7)M(-1) s(-1) at pH 7.4 and 25 degrees C, respectively). The reductive part of the catalytic cycle was also studied, and the rate constant for the reduction of c-TXNPx by tryparedoxin I was 1.3 x 10(6) M-1 s(-1). The catalytic role of two conserved cysteine residues in both TXNPxs was confirmed with the identification of Cys52 and Cys173 (in c-TXNPX) and Cys81 and Cys204 (in m-TXNPx) as the peroxidatic and resolving cysteines, respectively. Our results indicate that mitochondrial and cytosolic TXNPxs from T. cruzi are highly efficient peroxidases that reduce hydrogen peroxide and peroxynitrite, and contribute to the understanding of their role as virulence factors reported in vivo. (C) 2010 Elsevier Inc. All rights reserved.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.6
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

Editorial Material Multidisciplinary Sciences

In vivo observation of peroxiredoxins oligomerization dynamics

Ari Zeida, Bruno Manta, Madia Trujillo

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2020)

Article Biochemistry & Molecular Biology

Acidity and nucleophilic reactivity of glutathione persulfide

Dayana Benchoam, Jonathan A. Semelak, Ernesto Cuevasanta, Mauricio Mastrogiovanni, Juan S. Grassano, Gerardo Ferrer-Sueta, Ari Zeida, Madia Trujillo, Matias N. Moller, Dario A. Estrin, Beatriz Alvarez

JOURNAL OF BIOLOGICAL CHEMISTRY (2020)

Review Pharmacology & Pharmacy

Trypanothione Metabolism as Drug Target for Trypanosomatids

Maria Dolores Pineyro, Diego Arias, Adriana Parodi-Talice, Sergio Guerrero, Carlos Robello

Summary: Chagas Disease, African sleeping sickness, and leishmaniasis are neglected diseases caused by pathogenic trypanosomatid parasites, which have significant impact in poor countries. Current treatment drugs are toxic, difficult to access, and may lead to drug resistance. Inhibiting essential parasite metabolic pathways unique from the host can lead to more efficient and safe drug development.

CURRENT PHARMACEUTICAL DESIGN (2021)

Article Biochemistry & Molecular Biology

The effects of nitric oxide or oxygen on the stable products formed from the tyrosine phenoxyl radical

Lisa K. Folkes, Silvina Bartesaghi, Madia Trujillo, Peter Wardman, Rafael Radi

Summary: Tyrosine plays a critical role in proteins and can undergo oxidative modifications, producing phenoxyl radicals. The reactivity of tyrosine phenoxyl radicals with oxygen and nitric oxide differs significantly, with unclear products from these reactions. The fate of tyrosine phenoxyl radicals in biological systems is determined by the availability of oxidants and reductants.

FREE RADICAL RESEARCH (2021)

Meeting Abstract Biochemistry & Molecular Biology

Human peroxiredoxin 3: oxidizing substrate specificity, glutathionylation and other oxidative post-translational modifications

Madia Trujillo

FREE RADICAL BIOLOGY AND MEDICINE (2021)

Article Infectious Diseases

Maxicircle architecture and evolutionary insights into Trypanosoma cruzi complex

Luisa Berna, Gonzalo Greif, Sebastian Pita, Paula Faral-Tello, Florencia Diaz-Viraque, Rita De Cassia Moreira De Souza, Gustavo Adolfo Vallejo, Fernando Alvarez-Valin, Carlos Robello

Summary: This study sequenced maxicircles of T. cruzi strains using long-read sequencing technology, revealing a common architecture with four regions. Through phylogenetic analysis and comparison of genomic composition, it was found that T. cruzi is a complex of species composed of various maxicircle variants.

PLOS NEGLECTED TROPICAL DISEASES (2021)

Review Biochemistry & Molecular Biology

Radiolysis Studies of Oxidation and Nitration of Tyrosine and Some Other Biological Targets by Peroxynitrite-Derived Radicals

Lisa K. Folkes, Silvina Bartesaghi, Madia Trujillo, Peter Wardman, Rafael Radi

Summary: The use of free radicals in biology, particularly peroxynitrite-derived radicals, has attracted significant attention. This review discusses the principles and methods of selective radical generation by radiolysis, as well as the key reactions of peroxynitrite-derived radicals with potential biological targets. Additionally, studies involving the reactions of these radicals with lipoic acid/dihydrolipoic acid, hydrogen sulphide, and desferrioxamine are outlined.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

Review Physiology

THE SUPEROXIDE RADICAL SWITCH IN THE BIOLOGY OF NITRIC OXIDE AND PEROXYNITRITE

Lucia Piacenza, Ari Zeida, Madia Trujillo, Rafael Radi

Summary: The free radical nitric oxide (NO) plays a key role in physiological processes, but its bioavailability is compromised in certain disease conditions due to increased production of superoxide radical. This leads to the inactivation of nitric oxide and the formation of peroxynitrite, which is implicated in various human diseases and the aging process. Understanding the complex biochemistry of peroxynitrite is crucial for developing therapeutic interventions.

PHYSIOLOGICAL REVIEWS (2022)

Article Biochemistry & Molecular Biology

Profiling the Site of Protein CoAlation and Coenzyme A Stabilization Interactions

Maria-Armineh Tossounian, Maria Baczynska, William Dalton, Charlie Newell, Yilin Ma, Sayoni Das, Jonathan Alexis Semelak, Dario Ariel Estrin, Valeriy Filonenko, Madia Trujillo, Sew Yeu Peak-Chew, Mark Skehel, Franca Fraternali, Christine Orengo, Ivan Gout

Summary: Coenzyme A (CoA) plays a crucial role in metabolism and gene regulation. Recent studies have shown that CoA functions as an important antioxidant by forming a disulfide bond with proteins, called CoAlation. This study identified and classified CoAlated proteins from various organisms under stress conditions, and analyzed the stabilization interactions of CoA segments within the modified cysteines. The findings propose three modes of CoA binding to proteins and provide a comprehensive understanding of CoAlation proteins' functional distribution and CoA-protein stabilization interactions.

ANTIOXIDANTS (2022)

Review Biochemistry & Molecular Biology

Possible molecular basis of the biochemical effects of cysteine-derived persulfides

Ernesto Cuevasanta, Dayana Benchoam, Jonathan A. Semelak, Matias N. Moller, Ari Zeida, Madia Trujillo, Beatriz Alvarez, Dario A. Estrin

Summary: Persulfides are species closely related to thiols and hydrogen sulfide, and can be formed in biological systems. They act as key intermediates in catabolic and biosynthetic processes, and may impact the properties of biomolecules involved.

FRONTIERS IN MOLECULAR BIOSCIENCES (2022)

Meeting Abstract Biochemistry & Molecular Biology

Human peroxiredoxin 3 is rapidly oxidized and hyperoxidized by lipid hydroperoxides

Giuliana Cardozo, Mauricio Mastrogiovanni, Rafael Radi, Madia Trujillo, Anibal M. Reyes

FREE RADICAL BIOLOGY AND MEDICINE (2022)

Meeting Abstract Biochemistry & Molecular Biology

LsfA, a 1-Cys Peroxiredoxin involved with Pseudomonas aeruginosa virulence: Structure, biochemical activity, and its influence in inflammation/resolution

Rogerio Aleixo Silva, Renato Domingos, Madia Trujillo, Arnaldo Filho, Cristiano Oliveira, Regina Baldini, Jesmond Dalli, Luis Netto

FREE RADICAL BIOLOGY AND MEDICINE (2022)

Article Microbiology

New Insights into the Role of the Trypanosoma cruzi Aldo-Keto Reductase TcAKR

Florencia Diaz-Viraque, Maria Laura Chiribao, Lisvane Paes-Vieira, Matias R. Machado, Paula Faral-Tello, Ramiro Tomasina, Andrea Trochine, Carlos Robello

Summary: Chagas disease, caused by Trypanosoma cruzi, is a widespread infectious disease with no effective treatment. TcAKR, an enzyme involved in the metabolism of the anti-Chagas drugs benznidazole and nifurtimox, was found to have a biological role in the parasite mitochondria and potential involvement in PGF(2)alpha synthesis.

PATHOGENS (2023)

Article Microbiology

Genome-wide chromatin interaction map for Trypanosoma cruzi

Florencia Diaz-Viraque, Maria Laura Chiribao, Maria Gabriela Libisch, Carlos Robello

Summary: This study revealed the three-dimensional chromatin structure of the Trypanosoma cruzi genome using chromosome conformation capture (Hi-C) technology, showing the formation of C and D chromatin compartments by the core and disruptive regions. These chromatin compartments differ in DNA methylation levels, nucleosome positioning, and chromatin interactions, affecting genome expression dynamics.

NATURE MICROBIOLOGY (2023)

Article Microbiology

Overoxidation and Oligomerization of Trypanosoma cruzi Cytosolic and Mitochondrial Peroxiredoxins

Maria Dolores Pineyro, Maria Laura Chiribao, Diego G. Arias, Carlos Robello, Adriana Parodi-Talice

Summary: This study investigated the sensitivity and dynamics of Trypanosoma cruzi Prxs to overoxidation in vitro and in an infection context. The results showed that Prxs were overoxidized in parasites treated with oxidants, and the overoxidized forms remained present at least 24 hours after treatment. Overoxidation of Prxs was also observed in amastigotes residing in infected macrophages. Furthermore, the study found that m-TXNPx has a redox-state-dependent chaperone activity.

PATHOGENS (2023)

Article Biochemistry & Molecular Biology

Activation of the TGF-81/EMT signaling pathway by claudin-1 overexpression reduces doxorubicin sensitivity in small cell lung cancer SBC-3 cells

Yuri Nagaoka, Kotone Oshiro, Yuta Yoshino, Toshiyuki Matsunaga, Satoshi Endo, Akira Ikari

Summary: This study investigated the effect of intercellular adhesion molecule CLDN1 on the anticancer drug sensitivity of small-cell lung cancer (SCLC) cells. It was found that overexpression of CLDN1 decreased the sensitivity of SCLC cells to anticancer drugs and enhanced their migratory capacity through the activation of the TGF-81/EMT signaling pathway. Treatment with EMT inhibitors showed potential in overcoming the reduced sensitivity to anticancer drugs in CLDN1-overexpressing SCLC cells.

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS (2024)