Cardiotrophin-1 Induces the Same Neuropeptides in Sympathetic Neurons as Do Neuropoietic Cytokines


Address correspondence and reprint requests to Dr. P. H. Patterson at Division of Biology, California Institute of Technology, Pasadena, CA 91125, U.S.A.


Abstract: Cardiotrophin-1 (CT-1) was cloned from mouse embryoid body for its ability to induce growth of heart cells. Predictions of its secondary structure indicate that CT-1 belongs to a family of cytokines with a four-helical bundle structure, and sequence comparisons reveal a weak homology to leukemia inhibitory factor (LIF) and ciliary neurotrophic factor (CNTF). Using a reverse transcriptase-polymerase chain reaction assay with rat sympathetic neuron cultures, we find that CT-1 induces and suppresses the expression of the same set of neuropeptide and neurotransmitter synthetic enzyme mRNAs as do LIF and CNTF. In addition, the effects of CT-1 and LIF are not additive, and CT-1 does not require a GPI-linked component to mediate its actions. Our functional data confirm that CT-1 is a member of the neuropoietic cytokine family and suggest that the CT-1 receptor complex contains the gp130 signal transducing component.

Abbreviations used: CCK, cholecystokinin; CGRP, calcitonin gene-related peptide; ChAT, choline acetyltransferase; CNTF, ciliary neurotrophic factor; CT-1, cardiotrophin-1; DYN, dynorphin; ENK, enkephalin; GPA, growth-promoting activity; GPI, glycosylphosphatidylinositol; IL-6, interleukin-6; LIF, leukemia inhibitory factor; NGF, nerve growth factor; NPY, neuropeptide Y; OSM, oncostatin M; PI-PLC, phosphatidylinositol-specific phospholipase C; RT-PCR, reverse transcriptase-polymerase chain reaction; SOM, somatostatin; SP, substance P; TH, tyrosine hydroxylase; TPH, tryptophan hydroxylase; VIP, vasoactive intestinal polypeptide.