A Trypanosomal Protein Synergizes with the Cytokines Ciliary Neurotrophic Factor and Leukemia Inhibitory Factor to Prevent Apoptosis of Neuronal Cells
AUTOR(ES)
Chuenkova, Marina V.
FONTE
The American Society for Cell Biology
RESUMO
Despite the neuronal degeneration in the chronic stage of Chagas' disease, neuron counts actually increase in the preceding, asymptomatic stage, in contrast to the age-related decrease in neuron counts in age-matched normal individuals. Relevant to this observation, we found that the trans-sialidase (TS) of Trypanosoma cruzi, the etiologic agent of Chagas' disease, induces neurite outgrowth and rescues PC12 cells from apoptotic death caused by growth factor deprivation. These properties, novel for a parasite protein, were independent of catalytic activity and were mapped to the C terminus of the catalytic domain of TS. TS activated protein kinase Akt in a phosphoinositide-3 kinase-inhibitable manner, suggesting a molecular mechanism for the TS-induced neuroprotection. TS also triggered bcl-2 gene expression in growth factor-deprived cells, an effect consistent with TS protecting against apoptosis. Ciliary neurotrophic factor and leukemia inhibitory factor, two cytokines critical to the repair of injured motor neurons, specifically potentiated the TS action. The results suggest that TS acts in synergy with host ciliary neurotrophic factor or leukemia inhibitory factor to promote neuronal survival in T. cruzi-infected individuals.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=14861Documentos Relacionados
- Proliferative responses and binding properties of hematopoietic cells transfected with low-affinity receptors for leukemia inhibitory factor, oncostatin M, and ciliary neurotrophic factor.
- Detection of receptors for interleukin-6, interleukin-11, leukemia inhibitory factor, oncostatin M, and ciliary neurotrophic factor in bone marrow stromal/osteoblastic cells.
- Identification of ciliary neurotrophic factor (CNTF) residues essential for leukemia inhibitory factor receptor binding and generation of CNTF receptor antagonists.
- Isolation and characterization of the chicken m2 acetylcholine receptor promoter region: Induction of gene transcription by leukemia inhibitory factor and ciliary neurotrophic factor
- Neuroblastoma cells contain a trophic factor sharing biological and molecular properties with ciliary neurotrophic factor.