Apoptosis of Theileria-infected lymphocytes induced upon parasite death involves activation of caspases 9 and 3.
The intracellular parasite Theileria parva (T. parva) can infect bovine B and T-lymphocytes. T. parva-infected cells become transformed, and they survive and proliferate independently of exogenous growth factors. In vivo the uncontrolled cellular proliferation associated with lymphocyte transformation underlies the pathogenesis of the disease called East Coast Fever. The transformed state of parasitised cells can be reversed upon elimination of the parasite by specific theilericide drugs. In this study we found that elimination of the parasite by buparvaquone induces apoptosis of transformed B and CD8(+) T-lymphocytes. Apoptosis is accompanied by the activation of caspase 9 and caspase 3 and processing of poly(ADP ribose) polymerase and is inhibited by Z-VAD a general caspase inhibitor. Based on these observations, we propose that the lack of activation of a caspase 9 > caspase 3 > poly(ADP ribose) polymerase pathway is important and protects T. parva-transformed cells from spontaneous apoptosis.
Département de Parasitologie, URA CNRS 2581, Institut Pasteur, 25, rue du Dr Roux, 75015 Paris, France. guergnon@pasteur.fr
Julien
J
Guergnon
Frédéric
F
Dessauge
Gordon
G
Langsley
Alphonse
A
Garcia
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3; D053453:Caspase 9; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D002417:Cattle; D016923:Cell Death / Q000502:physiology; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004789:Enzyme Activation; D009285:Naphthoquinones / Q000494:pharmacology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000469:parasitology / Q000473:pathology*; D016797:Theileria parva / Q000187:drug effects / Q000472:pathogenicity*; D013801:Theileriasis / Q000469:parasitology / Q000473:pathology
D000590:Amino Acid Chloromethyl Ketones; D000981:Antiprotozoal Agents; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D009285:Naphthoquinones; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C046326:buparvaquone; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases