scholarly journals The Double-Edged Sword in Pathogenic Trypanosomatids: The Pivotal Role of Mitochondria in Oxidative Stress and Bioenergetics

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Rubem Figueiredo Sadok Menna-Barreto ◽  
Solange Lisboa de Castro
Keyword(s):  
Trypanosoma Brucei ◽  
Cell Signalling ◽  
Oxygen Species ◽  
Kinetoplast Dna ◽  
Excellent Candidate ◽  
Causative Agents ◽  
Parasite Biology ◽  
Oxidative Regulation ◽  
Single Mitochondrion

The pathogenic trypanosomatidsTrypanosoma brucei,Trypanosoma cruzi, andLeishmaniaspp. are the causative agents of African trypanosomiasis, Chagas disease, and leishmaniasis, respectively. These diseases are considered to be neglected tropical illnesses that persist under conditions of poverty and are concentrated in impoverished populations in the developing world. Novel efficient and nontoxic drugs are urgently needed as substitutes for the currently limited chemotherapy. Trypanosomatids display a single mitochondrion with several peculiar features, such as the presence of different energetic and antioxidant enzymes and a specific arrangement of mitochondrial DNA (kinetoplast DNA). Due to mitochondrial differences between mammals and trypanosomatids, this organelle is an excellent candidate for drug intervention. Additionally, during trypanosomatids’ life cycle, the shape and functional plasticity of their single mitochondrion undergo profound alterations, reflecting adaptation to different environments. In an uncoupling situation, the organelle produces high amounts of reactive oxygen species. However, these species role in parasite biology is still controversial, involving parasite death, cell signalling, or even proliferation. Novel perspectives on trypanosomatid-targeting chemotherapy could be developed based on better comprehension of mitochondrial oxidative regulation processes.

Timing of nuclear and kinetoplast DNA replication and early morphological events in the cell cycle of Trypanosoma brucei

1990 ◽  
Vol 95 (1) ◽  
pp. 49-57 ◽  
Author(s):  
R. Woodward ◽  
K. Gull
Keyword(s):  
Cell Cycle ◽  
Dna Replication ◽  
Trypanosoma Brucei ◽  
Basal Body ◽  
Unit Cell ◽  
Kinetoplast Dna ◽  
Interphase Cell ◽  
Body Formation ◽  
Timing Of Initiation ◽  
Single Mitochondrion

We have used immunofluorescent detection of 5-bromo-2-deoxyuridine-substituted DNA in order to determine the timing of initiation and the duration of nuclear and kinetoplast S-phases within the procyclic stage of the Trypanosoma brucei cell cycle. Both nuclear and kinetoplast S-phases were shown to be periodic, occupying 0.18 and 0.12 of the unit cell cycle, respectively. In addition, initiation of both of these S-phases were in approximate synchrony, differing by only 0.03 of the unit cell cycle. We have also used a monoclonal antibody that recognises the basal bodies of T. brucei in order to visualise cells possessing a new pro-basal body and hence determine the time of pro-basal body formation within the cell cycle. Pro-basal body formation occurred within a few minutes of the initiation of nuclear S-phase, at 0.41 of the unit cell cycle. This provides detection of the earliest known cell cycle event in T. brucei at the level of the light microscope. Cell cycle events including initiation of nuclear and kinetoplast DNA replication and pro-basal body formation may be strictly coordinated in T. brucei in order to maintain the precise single-mitochondrion (kinetoplast), singleflagellum status of the interphase cell.

scholarly journals Oxidative stress in marathon runners: interest of antioxidant supplementation

2006 ◽  
Vol 96 (S1) ◽  
pp. S31-S33 ◽  
Author(s):  
Mari-Carmen Gomez-Cabrera ◽  
Agustín Martínez ◽  
Gustavo Santangelo ◽  
Federico V. Pallardó ◽  
Juan Sastre ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Xanthine Oxidase ◽  
Cell Signalling ◽  
Reactive Oxygen ◽  
Peripheral Blood Lymphocytes ◽  
Signalling Pathways ◽  
Marathon Running ◽  
Oxygen Species ◽  
Marathon Runners

We have recently reported that xanthine oxidase is involved in the generation of free radicals in exhaustive exercise. Allopurinol, an inhibitor of xanthine oxidase, prevents it. The aim of the present work was to elucidate the role of exercise-derived reactive oxygen species in the cell signalling pathways involved in the adaptation to exercise in man. We have found that exercise causes an increase in the activity of plasma xanthine oxidase and an activation of NF-κB in peripheral blood lymphocytes after marathon running. This activation is dependent on free radical formation in exercise: treatment with allopurinol completely prevents it. In animal models, we previously showed that NF-κB activation induced by exhaustive physical exercise leads to an increase in the expression of superoxide dismutase, an enzyme involved in antioxidant defence. We report evidence in man that reactive oxygen species act as signals in exercise as decreasing their formation prevents activation of important signalling pathways which can cause useful adaptations in cells.

Myotubularins, PtdIns5P, and ROS in ABA-mediated stomatal movements in dehydrated Arabidopsis seedlings

2018 ◽  
Vol 45 (2) ◽  
pp. 259 ◽  
Author(s):  
Akanksha Nagpal ◽  
Ammar Hassan ◽  
Ivan Ndamukong ◽  
Zoya Avramova ◽  
František Baluška
Keyword(s):  
Cell Signalling ◽  
Membrane Dynamics ◽  
Dehydration Stress ◽  
Oxygen Species ◽  
Secondary Messenger ◽  
Signalling Molecule ◽  
Ros Accumulation ◽  
Evolutionarily Conserved ◽  
Stomatal Movements

Myotubularins (MTMs) are lipid phosphoinositide 3-phosphate phosphatases and the product of their enzyme activity – phosphoinositide 5-phosphate (PtdIns5P) – functions as a signalling molecule in pathways involved in membrane dynamics and cell signalling. Two Arabidopsis genes, AtMTM1 and AtMTM2, encode enzymatically active phosphatases but although AtMTM1 deficiency results in increased tolerance to dehydration stress and a decrease in cellular PtdIns5P, the role of AtMTM2 is less clear, as it does not contribute to the PtdIns5P pool upon dehydration stress. Here we analysed the involvement of AtMTM1, AtMTM2 and PtdIns5P in the response of Arabidopsis seedlings to dehydration stress/ABA, and found that both AtMTM1 and AtMTM2 were involved but affected oppositely stomata movement and the accumulation of reactive oxygen species (ROS, e.g. H2O2). Acting as a secondary messenger in the ABA-induced ROS production in guard cells, PtdIns5P emerges as an evolutionarily conserved signalling molecule that calibrates cellular ROS under stress. We propose the biological relevance of the counteracting AtMTM1 and AtMTM2 activities is to balance the ABA-induced ROS accumulation and cellular homeostasis under dehydration stress.

Analysis of radicals and radical reaction products in cell signalling and biomolecular damage: the long hard road to gold-standard measures

2011 ◽  
Vol 39 (5) ◽  
pp. 1217-1220 ◽  
Author(s):  
Paul G. Winyard ◽  
Corinne M. Spickett ◽  
Helen R. Griffiths
Keyword(s):  
Free Radical ◽  
Cell Signalling ◽  
Radical Reaction ◽  
Research Area ◽  
Oxygen Species ◽  
Reaction Products ◽  
Research Areas ◽  
Key Factor ◽  
Topical Interest

The field of free radical biology and medicine continues to move at a tremendous pace, with a constant flow of ground-breaking discoveries. The following collection of papers in this issue of Biochemical Society Transactions highlights several key areas of topical interest, including the crucial role of validated measurements of radicals and reactive oxygen species in underpinning nearly all research in the field, the important advances being made as a result of the overlap of free radical research with the reinvigorated field of lipidomics (driven in part by innovations in MS-based analysis), the acceleration of new insights into the role of oxidative protein modifications (particularly to cysteine residues) in modulating cell signalling, and the effects of free radicals on the functions of mitochondria, extracellular matrix and the immune system. In the present article, we provide a brief overview of these research areas, but, throughout this discussion, it must be remembered that it is the availability of reliable analytical methodologies that will be a key factor in facilitating continuing developments in this exciting research area.

scholarly journals Role of p38 in Replication of Trypanosoma brucei Kinetoplast DNA

2006 ◽  
Vol 26 (14) ◽  
pp. 5382-5393 ◽  
Author(s):  
Beiyu Liu ◽  
Henrik Molina ◽  
Dario Kalume ◽  
Akhilesh Pandey ◽  
Jack D. Griffith ◽  
...  
Keyword(s):  
Rna Interference ◽  
Dna Replication ◽  
Mitochondrial Genome ◽  
Dna Synthesis ◽  
Trypanosoma Brucei ◽  
Replication Origin ◽  
Mitochondrial Protein ◽  
Kinetoplast Dna ◽  
Z Dna

ABSTRACT Trypanosomes have an unusual mitochondrial genome, called kinetoplast DNA, that is a giant network containing thousands of interlocked minicircles. During kinetoplast DNA synthesis, minicircles are released from the network for replication as θ-structures, and then the free minicircle progeny reattach to the network. We report that a mitochondrial protein, which we term p38, functions in kinetoplast DNA replication. RNA interference (RNAi) of p38 resulted in loss of kinetoplast DNA and accumulation of a novel free minicircle species named fraction S. Fraction S minicircles are so underwound that on isolation they become highly negatively supertwisted and develop a region of Z-DNA. p38 binds to minicircle sequences within the replication origin. We conclude that cells with RNAi-induced loss of p38 cannot initiate minicircle replication, although they can extensively unwind free minicircles.

scholarly journals Cell signalling by oxidized lipids and the role of reactive oxygen species in the endothelium

2005 ◽  
Vol 33 (6) ◽  
pp. 1385 ◽  
Author(s):  
A. Landar ◽  
J.W. Zmijewski ◽  
N. Watanabe ◽  
D.A. Dickinson ◽  
N. Noguchi ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Signalling ◽  
Reactive Oxygen ◽  
Oxidized Lipids ◽  
Oxygen Species

Trypanocidal drugs: mechanisms, resistance and new targets

2009 ◽  
Vol 11 ◽  
Author(s):  
Shane R. Wilkinson ◽  
John M. Kelly
Keyword(s):  
Trypanosoma Brucei ◽  
Chemotherapeutic Agents ◽  
Protozoan Parasites ◽  
Health Burden ◽  
Limited Efficacy ◽  
New Findings ◽  
Causative Agents ◽  
Parasite Biology ◽  
New Research ◽  
Trypanocidal Drugs

The protozoan parasitesTrypanosoma bruceiandTrypanosoma cruziare the causative agents of African trypanosomiasis and Chagas disease, respectively. These are debilitating infections that exert a considerable health burden on some of the poorest people on the planet. Treatment of trypanosome infections is dependent on a small number of drugs that have limited efficacy and can cause severe side effects. Here, we review the properties of these drugs and describe new findings on their modes of action and the mechanisms by which resistance can arise. We further outline how a greater understanding of parasite biology is being exploited in the search for novel chemotherapeutic agents. This effort is being facilitated by new research networks that involve academic and biotechnology/pharmaceutical organisations, supported by public–private partnerships, and are bringing a new dynamism and purpose to the search for trypanocidal agents.

Role of reactive oxygen species in cell signalling pathways

2001 ◽  
Vol 29 (2) ◽  
pp. 345-349 ◽  
Author(s):  
J. T. Hancock ◽  
R. Desikan ◽  
S.J. Neill
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Signalling ◽  
Reactive Oxygen ◽  
Signalling Pathways ◽  
Oxygen Species ◽  
Phagocytic Cells ◽  
Mitogen Activated Protein ◽  
A Cell ◽  
Activate Cell

Reactive oxygen species (ROS) were originally thought to only be released by phagocytic cells during their role in host defence. It is now clear that ROS have a cell signalling role in many biological systems, both in animals and in plants. ROS induce programmed cell death or necrosis, induce or suppress the expression of many genes, and activate cell signalling cascades, such as those involving mitogen-activated protein kinases.

scholarly journals Role of the inhibitor of serine peptidase 2 (ISP2) of Trypanosoma brucei rhodesiense in parasite virulence and modulation of the inflammatory responses of the host

2021 ◽  
Vol 15 (6) ◽  
pp. e0009526
Author(s):  
David Jessula Levy ◽  
Amy Goundry ◽  
Raquel S. S. Laires ◽  
Tatiana F. R. Costa ◽  
Carlos Mendes Novo ◽  
...  
Keyword(s):  
Trypanosoma Brucei ◽  
Inflammatory Responses ◽  
Trypanosoma Brucei Rhodesiense ◽  
Lower Blood ◽  
Tnf Α ◽  
Causative Agents ◽  
The Central Nervous System ◽  
Two Peaks

Trypanosoma brucei rhodesiense is one of the causative agents of Human African Trypanosomiasis (HAT), known as sleeping sickness. The parasite invades the central nervous system and causes severe encephalitis that is fatal if left untreated. We have previously identified ecotin-like inhibitors of serine peptidases, named ISPs, in trypanosomatid parasitic protozoa. Here, we investigated the role of ISP2 in bloodstream form T. b. rhodesiense. We generated gene-deficient mutants lacking ISP2 (Δisp2), which displayed a growth profile in vitro similar to that of wild-type (WT) parasites. C57BL/6 mice infected with Δisp2 displayed lower blood parasitemia, a delayed hind leg pathological phenotype and survived longer. The immune response was examined at two time-points that corresponded with two peaks of parasitemia. At 4 days, the spleens of Δisp2-infected mice had a greater percentage of NOS2+ myeloid cells, IFN-γ+-NK cells and increased TNF-α compared to those infected with WT and parasites re-expressing ISP2 (Δisp2:ISP2). By 13 days the increased NOS2+ population was sustained in Δisp2-infected mice, along with increased percentages of monocyte-derived dendritic cells, as well as CD19+ B lymphocytes, and CD8+ and CD4+ T lymphocytes. Taken together, these findings indicate that ISP2 contributes to T. b. rhodesiense virulence in mice and attenuates the inflammatory response during early infection.

Impact of oxidative stress on male fertility — A review

2011 ◽  
Vol 59 (4) ◽  
pp. 465-484 ◽  
Author(s):  
Eva Tvrdá ◽  
Zuzana Kňažická ◽  
László Bárdos ◽  
Péter Massányi ◽  
Norbert Lukáč
Keyword(s):  
Oxidative Stress ◽  
Male Fertility ◽  
Cell Signalling ◽  
Cellular Damage ◽  
Signalling Pathways ◽  
Oxygen Species ◽  
Oxygen Derived Free Radicals ◽  
Enzymatic Systems

Oxidative stress is a state related to increased cellular damage caused by oxygen and oxygen-derived free radicals known as reactive oxygen species (ROS). It is a serious condition, as ROS and their metabolites attack DNA, lipids and proteins, alter enzymatic systems and cell signalling pathways, producing irreparable alterations, cell death and necrosis. While small amounts of ROS have been shown to be required for several functions of spermatozoa, their excessive levels can negatively impact the quality of spermatozoa and impair their overall fertilising capacity. These questions have recently attracted the attention of the scientific community; however, research aimed at exploring the role of oxidative stress and antioxidants associated with male fertility is still at its initial stages. This review summarises the current facts available in this field and intends to stimulate interest in basic and clinical research, especially in the development of effective methods for the diagnosis and therapy of semen damage caused by oxidative stress.

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