title: The AMPKα1 Pathway Positively Regulates the Developmental Transition from Proliferation to Quiescence in Trypanosoma brucei.
abstract: During infection in mammals, the protozoan parasite Trypanosoma brucei transforms from a proliferative bloodstream form to a quiescent form that is pre-adapted to host transition. AMP analogs are known to induce quiescence and also inhibit TbTOR4. To examine the role of AMP-activated kinase (AMPK) in the regulation of this developmental transition, we characterized trypanosome TbAMPK complexes. Expression of a constitutively active AMPKα1 induces quiescence of the infective form, and TbAMPKα1 phosphorylation occurs during differentiation of wild-type pleomorphic trypanosomes to the quiescent stumpy form in vivo. Compound C, a well-known AMPK inhibitor, inhibits parasite differentiation in mice. We also provide evidence linking oxidative stress to TbAMPKα1 activation and quiescent differentiation, suggesting that TbAMPKα1 activation balances quiescence, proliferation, and differentiation.
authors.affiliation: Instituto de Parasitología y Biomedicina López-Neyra, Consejo Superior de Investigaciones Científicas, Avenida del Conocimiento s/n, 18016 Granada, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Saldivia
authors.affiliation: Instituto de Parasitología y Biomedicina López-Neyra, Consejo Superior de Investigaciones Científicas, Avenida del Conocimiento s/n, 18016 Granada, Spain.
authors.forename: Gloria
authors.initials: G
authors.lastname: Ceballos-Pérez
authors.affiliation: Instituto de Parasitología y Biomedicina López-Neyra, Consejo Superior de Investigaciones Científicas, Avenida del Conocimiento s/n, 18016 Granada, Spain.
authors.forename: Jean-Mathieu
authors.initials: JM
authors.lastname: Bart
authors.affiliation: Instituto de Parasitología y Biomedicina López-Neyra, Consejo Superior de Investigaciones Científicas, Avenida del Conocimiento s/n, 18016 Granada, Spain. Electronic address: miguel.navarro@ipb.csic.es.
authors.forename: Miguel
authors.initials: M
authors.lastname: Navarro
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000249:Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D008807:Mice, Inbred BALB C; D018384:Oxidative Stress / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D014346:Trypanosoma brucei brucei / Q000166:cytology* / Q000201:enzymology*; D014352:Trypanosomiasis / Q000469:parasitology / Q000473:pathology
chemical_list: D000249:Adenosine Monophosphate; D055372:AMP-Activated Protein Kinases
keywords: AMPK; GSK3; ROS; TOR; Trypanosoma brucei; developmental differentiation; quiescence; trypanosome stumpy form