Induction of apoptosis in cerebellar granule cells by 2,4-dichlorophenoxyacetic acid.
2,4-Dichlorophenoxyacetic acid (2,4-D) and derivatives are herbicides widely used in Argentina and other parts of the world. Exposure to 2,4-D, its ester and salt formulations, have been associated with a range of adverse health effects in humans and different animal species, from embryotoxicity and teratogenicity to neurotoxicity. In this work, we demonstrate that after 24 hs of treatment with 1 and 2 mM 2,4-D there is an induction of apoptosis in cerebellar granule cells (CGC) in culture. However, with 2 mM 2,4-D one population of CGC developed features of apoptosis while another appeared to die by necrosis. This process is associated with an increase in caspase-3 activity after 12 hs of treatment with the herbicide, which is preceded by cytochrome c release from the mitochondria. Treatment of CGC with 2,4-D appears to induce apoptosis by a direct effect on mitochondria producing cytochrome c release and consequently activation of caspase-3, being mitochondrial damage sufficient for triggering the events that may cause apoptosis.
De Moliner
K L
KL
Departamento de Química Biológica. IQUIFIB, Universidad de Buenos Aires, CONICET, Junín 956, Buenos Aires (1113), Argentina.
Evangelista de Duffard
A M
AM
Soto
E
E
Duffard
R
R
Adamo
A M
AM
D015084:2,4-Dichlorophenoxyacetic Acid / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D003574:Cytochrome c Group / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000187:drug effects* / Q000201:enzymology; D004789:Enzyme Activation; D006540:Herbicides / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D003574:Cytochrome c Group; D006540:Herbicides; D015084:2,4-Dichlorophenoxyacetic Acid; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases