Mechanisms of p,p′-DDE-induced apoptosis in human peripheral blood mononuclear cells

Jorge A. Alegría-Torres, Fernando Díaz-Barriga, A Jay Gandolfi, Iván N. Pérez-Maldonado

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

p,p′-Dichlorodiphenyldichloroethylene (DDE), the most stable metabolite of organochlorine insecticide p,p′-dichlorodiphenyltrichloroethane (DDT), has been detected in human populations living in malaria-endemic areas of México where this insecticide was used. DDE induces apoptosis in peripheral blood mononuclear cells (PMBC); however, the molecular mechanism of cell death induced by this compound is poorly understood. In the present study, PBMC isolated from healthy individuals (not exposed to DDE) were incubated in the presence of increasing concentrations of p,p′-DDE (0-80 μg/ml) over time. When PBMC were treated with low p,p′-DDE concentration (10 μg/ml) an antioxidant response and biomarkers of inflammation were induced, indicating a pro-inflammatory state. Moreover, when PBMC were treated with high p,p′-DDE concentration (80 μg/ml) several apoptotic biochemical events were triggered, such as activation of caspase-8, Bid, caspase-9 and caspase-3, as well as degradation of PARP and ubiquitination. The results described in this study show a possible inflammatory condition and the involvement of both extrinsic and intrinsic pathways in the induction of apoptosis in DDE-treated PBMC.

Original languageEnglish (US)
Pages (from-to)1000-1006
Number of pages7
JournalToxicology in Vitro
Volume23
Issue number6
DOIs
StatePublished - Sep 2009

Fingerprint

Dichlorodiphenyl Dichloroethylene
Blood Cells
Blood
Apoptosis
Insecticides
Caspase 9
Caspase 8
Ubiquitination
Biomarkers
Cell death
Metabolites
Caspase 3
Malaria
Cell Death
Antioxidants
Chemical activation
Inflammation
Degradation
Population

Keywords

  • Apoptosis
  • p,p′-DDE
  • Pro-inflammatory state

ASJC Scopus subject areas

  • Toxicology

Cite this

Mechanisms of p,p′-DDE-induced apoptosis in human peripheral blood mononuclear cells. / Alegría-Torres, Jorge A.; Díaz-Barriga, Fernando; Gandolfi, A Jay; Pérez-Maldonado, Iván N.

In: Toxicology in Vitro, Vol. 23, No. 6, 09.2009, p. 1000-1006.

Research output: Contribution to journalArticle

Alegría-Torres, Jorge A. ; Díaz-Barriga, Fernando ; Gandolfi, A Jay ; Pérez-Maldonado, Iván N. / Mechanisms of p,p′-DDE-induced apoptosis in human peripheral blood mononuclear cells. In: Toxicology in Vitro. 2009 ; Vol. 23, No. 6. pp. 1000-1006.
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