A trypanosomal protein synergizes with the cytokines ciliary neurotrophic factor and leukemia inhibitory factor to prevent apoptosis of neuronal cells.
نویسندگان
چکیده
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.
منابع مشابه
Ciliary neurotrophic factor maintains the pluripotentiality of embryonic stem cells.
Ciliary neurotrophic factor was discovered based on its ability to support the survival of ciliary neurons, and is now known to act on a variety of neuronal and glial populations. Two distant relatives of ciliary neurotrophic factor, leukemia inhibitory factor and oncostatin M, mimic ciliary neurotrophic factor with respect to its actions on cells of the nervous system. In contrast to ciliary n...
متن کاملCytokine-Induced Nuclear Factor Kappa B Activation Promotes the Survival of Developing Neurons
Ciliary neurotrophic factor (CNTF), leukemia inhibitory factor (LIF), cardiotrophin-1 (CT-1), and interleukin 6 (IL-6) comprise a group of structurally related cytokines that promote the survival of subsets of neurons in the developing peripheral nervous system, but the signaling pathways activated by these cytokines that prevent neuronal apoptosis are unclear. Here, we show that these cytokine...
متن کامل3 CNTF and Related Neurokines
Ciliary neurotrophic factor (CNTF) is a member of the neurokine family of cytokines with actions on multiple cell types of the nervous system. CNTF shares a common gp130 receptor subunit with the other neurokines, leukemia inhibitory factor (LIF), interleukin‐6 (IL‐6), interleukin‐11 (IL‐11), cardiotrophin‐1 (CT‐1), oncostatin‐M (OSM), cardiotrophin‐like cytokine (CLC), and neuropoietin. Neurok...
متن کاملNuclear Factor-κb to the Rescue of Cytokine-Induced Neuronal Survival
Address correspondence to Patrik Ernfors, Lab. Mol. Neurobiol., MBB, Karolinska Institutet, Brezeliusväg 3, plan 3, 171 77 Stockholm, Sweden. Tel.: 46 8 728 7659. Fax: 46 8 728 76 56. E-mail: [email protected] During the development of the vertebrate nervous system, a balance is maintained between the formation of neurons and their synapses and neuronal death and synaptic remodeling. Neuro...
متن کاملCytokine-induced Neuronal Survival
Address correspondence to Patrik Ernfors, Lab. Mol. Neurobiol., MBB, Karolinska Institutet, Brezeliusväg 3, plan 3, 171 77 Stockholm, Sweden. Tel.: 46 8 728 7659. Fax: 46 8 728 76 56. E-mail: [email protected] During the development of the vertebrate nervous system, a balance is maintained between the formation of neurons and their synapses and neuronal death and synaptic remodeling. Neuro...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Molecular biology of the cell
دوره 11 4 شماره
صفحات -
تاریخ انتشار 2000