Redox Paradox: The Contribution of Reactive Oxygen Species (ROS) in the Proliferation and Differentiation of Trypanosoma cruzi

quantitatively measure mitochondrial network features in

this phenomenon is accompanied by a marked time and

cells treated with E2 or the selective estrogen receptor-α

concentration dependent increase in ROS formation and the

and β modulators (SERMs) propylpyrazole triol (PPT) and

modulation of epimastigotes mitochondrial physiology in an

diarylpropionitrile (DPN), respectively. 48h treatment of

effort to increase ROS as a metabolic mechanism to

mouse C2C12 myoblasts with various concentrations of

maintain

either E2 or DPN, but not PPT, significantly modified

Conversely, the antioxidants reverse the heme-induced ROS

mitochondrial network morphology. Both E2 and DPN

and

approximately

mitochondrial

Following the cycle, when these forms are taken into the

networks as well as the number of branches per network,

hindgut of the triatomine they return to the non-replicative,

while PPT had no effect on these parameters. Similarly, both

infective form, the metacyclic trypomastigotes. During the

E2 and DPN significantly increased the mitochondrial

metacyclogenesis,

footprint, a measure of mitochondrial abundance, while PPT

increment of trypomastigotes. These data gives us the idea

failed to modulate this feature. These data indicate that ER-

of

doubled

the

number

of

epimastigote

dramatically

a

“shift”

survival

impair

proliferation.

epimastigotes

antioxidants

between

and

induce

proliferation

to

proliferation.

a

significant

differentiation

β agonists strongly promote mitochondrial fusion. Thus,

according to the influence of the redox status. Surprisingly,

these observations provide initial quantitative evidence of

when metacyclic trypomastigotes are released into the insect

beneficial

feces the infection is again favored by ROS since inhibitors

actions

of

SERMs

such

as

DPN

as

a

pharmacological tool for targeting mitochondrial fusion in

of Nox and antioxidants greatly decrease macrophage

pathological

deficient

infection. Moreover, while the parasite needs oxidants for its

certain

proliferation inside the vector, the opposite occurs during its

conditions

mitochondrial

network

characterized formation,

such

by as

neurodegenerative diseases and cancers.

development inside the vertebrate host. H2O2 diminishes amastigotes proliferation and increases the trypomastigote

DOI: 10.1016/j.freeradbiomed.2017.10.269

differentiation into amastigotes. Taken together, our data reveal a redox paradox in which ROS plays antagonistic roles along Trypanosoma cruzi life cycle demonstrating a high capacity to adapt to its habitats.

257

DOI: 10.1016/j.freeradbiomed.2017.10.270

Redox Paradox: The Contribution of Reactive Oxygen Species (ROS) in the Proliferation and Differentiation of

258

Trypanosoma cruzi Natalia Nogueira1, Francis Saraiva1, Jessica Oliveira1, Gustavo Laranja1, Elmo Almeida-Amaral2, Georgia Atella3, Marcus Oliveira , and Marcia Paes 3

1

1

University of State of Rio de Janeiro -UERJ, Brazil

2

IOC - FIOCRUZ, Brazil

3

Federal University of Rio de Janeiro - UFRJ, Brazil

Poldip2 is an Oxygen-sensitive Mitochondrial Protein that Controls Oxidative/glycolytic Metabolism Balance and Proteasome Activity Felipe Paredes1, Holly Williams1, and Alejandra San Martin1

Trypanosoma cruzi is a protozoan that causes Chagas disease

1

Emory University, USA

or American trypanosomiasis. The parasite has a heteroxenic biological cycle developing between a vertebrate host

The polymerase delta interacting protein 2 (Poldip2) is a

(mammal) and an invertebrate (insect vector). The first

nuclear-encoded

environment encountered by T. cruzi after the blood meal is

function.

the midgut of the insect, where large amounts of

under hypoxia and that its deficiency results in repressed

hemoglobin are degraded resulting in the release of huge

mitochondrial function and increased glycolytic activity.

concentrations of heme, a molecule known to increase the

However, the mechanisms responsible for this metabolic

formation of ROS. Heme induces T. cruzi proliferation, and

reprograming and its consequences are unknown. In this

SfRBM 2017

mitochondrial

protein

of

unknown

We recently reported that Poldip2 is repressed

173