PMID- 24714638
OWN - NLM
STAT- MEDLINE
DCOM- 20150106
LR  - 20240109
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 9
IP  - 4
DP  - 2014
TI  - Trypanosoma cruzi cell death induced by the Morita-Baylis-Hillman adduct 
      3-Hydroxy-2-methylene-3-(4-nitrophenylpropanenitrile).
PG  - e93936
LID - 10.1371/journal.pone.0093936 [doi]
LID - e93936
AB  - Chagas disease, caused by the protozoan Trypanosoma cruzi, remains a serious 
      health concern due to the lack of effective vaccines or satisfactory treatment. 
      In the search for new compounds against this neglected disease, we have 
      previously demonstrated that the compound 
      3-Hydroxy-2-methylene-3-(4-nitrophenylpropanenitrile) (MBHA3), derived from the 
      Morita-Baylis-Hillman reaction, effectively caused a loss of viability in both 
      the epimastigote and trypomastigote forms. However, the mechanisms of parasite 
      death elicited by MBHA3 remain unknown. The aim of this study was to better 
      understand the morphophysiological changes and the mechanism of cell death 
      induced by MBHA3 treatment on T. cruzi. To perform this analysis, we used 
      confocal microscopy and flow cytometry to monitor the fluorescent probes such as 
      annexin-V/propidium iodide (AV/PI), calcein-AM/ethidium homodimer (CA/EH), 
      acridine orange (AO) and rhodamine 123 (Rho 123). Lower concentrations of MBHA3 
      led to alterations in the mitochondrial membrane potential and AO labeling, but 
      did not decrease the viability of the epimastiogote forms, as determined by the 
      CA/EH and AV/PI assays. Conversely, treatment with higher concentrations of MBHA3 
      led to extensive plasma membrane damage, loss of mitochondrion membrane 
      potential, DNA fragmentation and acidification of the cytoplasm. Our findings 
      suggest that at higher concentrations, MBHA3 induces T. cruzi epimastigote death 
      by necrosis in a mitochondrion-dependent manner.
FAU - Sandes, Jana M
AU  - Sandes JM
AD  - Departamento de Microbiologia, Centro de Pesquisas Aggeu Magalhaes, Recife, PE, 
      Brazil.
FAU - Fontes, Adriana
AU  - Fontes A
AD  - Departamento de Biofisica e Radiobiologia, Universidade Federal de Pernambuco, 
      Recife, PE, Brazil.
FAU - Regis-da-Silva, Carlos G
AU  - Regis-da-Silva CG
AD  - Laboratorio de Biologia Parasitaria, Centro Pesquisas Goncalo Moniz, Salvador, 
      BA, Brazil.
FAU - de Castro, Maria C A Brelaz
AU  - de Castro MC
AD  - Departamento de Imunologia, Centro de Pesquisas Aggeu Magalhaes, Recife, PE, 
      Brazil.
FAU - Lima-Junior, Claudio G
AU  - Lima-Junior CG
AD  - LASOM-PB, Departamento de Quimica, Universidade Federal da Paraiba, Joao Pessoa, 
      PB, Brazil.
FAU - Silva, Fabio P L
AU  - Silva FP
AD  - LASOM-PB, Departamento de Quimica, Universidade Federal da Paraiba, Joao Pessoa, 
      PB, Brazil.
FAU - Vasconcellos, Mario L A A
AU  - Vasconcellos ML
AD  - LASOM-PB, Departamento de Quimica, Universidade Federal da Paraiba, Joao Pessoa, 
      PB, Brazil.
FAU - Figueiredo, Regina C B Q
AU  - Figueiredo RC
AD  - Departamento de Microbiologia, Centro de Pesquisas Aggeu Magalhaes, Recife, PE, 
      Brazil.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140408
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (3-hydroxy-2-methylene-3-(4-nitrophenyl)propanenitrile)
RN  - 0 (Benzyl Alcohols)
RN  - 0 (Nitriles)
RN  - MP1U0D42PE (Acrylonitrile)
SB  - IM
MH  - Acrylonitrile/*analogs & derivatives/pharmacology/therapeutic use
MH  - Benzyl Alcohols/*pharmacology/therapeutic use
MH  - Cell Death/*drug effects
MH  - Cell Membrane/drug effects
MH  - Chagas Disease/*drug therapy/parasitology
MH  - Cytoplasm/drug effects
MH  - Membrane Potential, Mitochondrial/drug effects
MH  - Microscopy, Confocal
MH  - Nitriles
MH  - Trypanosoma cruzi/*drug effects
PMC - PMC3979736
COIS- Competing Interests: The authors have declared that no competing interest exist.
EDAT- 2014/04/10 06:00
MHDA- 2015/01/07 06:00
PMCR- 2014/04/08
CRDT- 2014/04/10 06:00
PHST- 2014/01/14 00:00 [received]
PHST- 2014/03/09 00:00 [accepted]
PHST- 2014/04/10 06:00 [entrez]
PHST- 2014/04/10 06:00 [pubmed]
PHST- 2015/01/07 06:00 [medline]
PHST- 2014/04/08 00:00 [pmc-release]
AID - PONE-D-14-01984 [pii]
AID - 10.1371/journal.pone.0093936 [doi]
PST - epublish
SO  - PLoS One. 2014 Apr 8;9(4):e93936. doi: 10.1371/journal.pone.0093936. eCollection 
      2014.