Disease relevance of Ctf1

• The treatment with adenovirus encoding CNTF, CT1 or IGF1, however, failed to protect these neurons after avulsion [1].
• Moreover, we also investigated, for the first time whether CT-1 and urocortin can induce hypertrophy in cultured adult as opposed to neonatal cardiac cells [2].
• Although tetanus toxin accumulated rapidly (within 8 h) at presynaptic sites, GDNF accumulated at synapses more slowly (within 15 h), and CT-1 never associated with synapses [3].
• These findings suggest that IL-6 and LIF, but not CT-1, contribute to angiotensin II-dependent left ventricular hypertrophy in the two hypertensive rat models, TGR(mRen2)27 and SHR [4].
• We suggest that CT-1 might facilitate LVH in genetic hypertension through a cross-talk with the renin-angiotensin system [5].

High impact information on Ctf1

• Several members of this family that are known to signal through the transmembrane protein gp130 stimulate cardiac myocyte hypertrophy, like cardiotrophin 1, suggesting that the gp130 signaling pathway may play a role in cardiac hypertrophy [6].
• Furthermore, the stimulation of isolated rat hepatocytes with CT-1 increased COX-1, COX-2, and VEGF messenger RNAs and prostaglandin synthesis [7].
• These changes were associated with downregulation of CT-1 and COX-1 and altered pattern of VEGF expression [7].
• Conversely, the addition of prostaglandin E1 to the culture increased CT-1 and VEGF production [7].
• Interplay among cardiotrophin-1, prostaglandins, and vascular endothelial growth factor in rat liver regeneration [7].

Chemical compound and disease context of Ctf1

• We studied the effects of CT-1 (100 microgram/kg ip, 10 min prior to ETX) in a rat model of ETX-induced acute lung injury (Salmonella typhimurium lipopolysaccharide, 20 mg/kg ip) [8].
• Administration of an adenovirus encoding CT-1 to NS-398-treated rats restituted normal levels of COX-1, prostaglandins, and VEGF in the liver after partial hepatectomy and restored normal liver regeneration [7].
• Finally, losartan, an angiotensin II type 1 receptor antagonist, significantly attenuated cardiotrophin-1-induced hypertrophy of neonatal rat cardiac myocytes [9].
• The effects of PGF2 alpha were compared with several known cardiac myocyte hypertrophy factors (phenylephrine, endothelin-1, leukemia inhibitory factor, cardiotrophin-1, and angiotensin II) [10].

Biological context of Ctf1

• CT-1 is released from the heart in response to hypoxic stress, and it protects cardiac myocytes from hypoxia-induced apoptosis, thus establishing a central role for this cytokine in the cardiac stress response [11].
• Together, the inhibitors completely blocked CT-1-dependent NF-kappa B activation and cytoprotection [11].
• CT-1 also induced the degradation of the NF-kappa B cytosolic anchor, I kappa B, as well as the translocation of the p65 subunit of NF-kappa B to the nucleus and increased expression of an NF-kappa B-dependent reporter gene [11].
• Overexpression of dominant-negative STAT3 mutant suppressed CT-1-induced STAT3 phosphorylation, but did not affect cell hypertrophy [12].
• These findings reveal a specific cell-broadening effect of CT-1 in cardiomyocytes from adult SHR and suggest that the hypertensive phenotype of these cells may influence the hypertrophic effects of CT-1, probably by means of an exaggerated induction of angiotensinogen expression [5].

Anatomical context of Ctf1

• We investigated whether urocortin is also hypertrophic in cardiac myocytes and whether it shares a common pathway with CT-1 for this effect [2].
• GDNF and CT-1, therefore, are major components of the trophic support provided by the Schwann and muscle cells, respectively [13].
• Levels of oncostatin M (OSM), leukemia inhibitory factor (LIF), cardiotrophin-1, and ciliary neurotrophic factor were all increased in the hippocampus after seizure, though to differing extents and with markedly different time courses [14].
• CT-1 induced cardiac fibroblast protein synthesis and proliferation [15].
• CT-1 abrogated the endotoxin-induced lung neutrophil accumulation: 2.3 +/- 0.2 units MPO/g wet lung (gwl) vs 6 [8].

Associations of Ctf1 with chemical compounds

• The cytoprotective effects of the glycoprotein 130 receptor-coupled cytokine, cardiotrophin-1, require activation of NF-kappa B [11].
• CT-1 increased c-fos and ANP expression (p<0.01) and cell area (p<0.01) in cardiomyocytes from both rat strains [5].
• Hepatocyte growth factor and cardiotrophin-1 mRNA expression was upregulated on embryonic day 12.5 and 15.5 in bis-diamine-treated hearts [16].
• Moreover, chronic CT-1 treatment resulted in the development of insulin resistance as judged by a decrease in insulin-stimulated glucose uptake [17].
• Tyrosine phosphorylation of STAT3 by cardiotrophin-1 treatment resulted in STAT3 homodimer binding to the St-domain in the angiotensinogen gene promoter, which lead to promoter activation in a transient transfection assay [9].

Regulatory relationships of Ctf1

• These results identify urocortin as a novel hypertrophic and protective agent whose hypertrophic effect is mediated by a distinct pathway to that activated by CT-1, although the two factors mediate protection via the same pathway [2].
• In the present study, CT-1 activated p38 and ERK MAPKs as well as Akt in cultured cardiac myocytes; these three pathways were activated in a parallel manner [11].
• CT-1 also induced phosphorylations of ERK1/2 and ERK5 in cardiomyocytes, and those, too, were suppressed by overexpression of SOCSs [12].
• In that regard, cardiotrophin-1 (CT-1) activates several signaling pathways via gp130, and induces hypertrophy in neonatal rat cardiomyocytes [12].
• BACKGROUND: Suppressor of cytokine signaling 1 (SOCS1) is a negative regulator of cytokine signaling whose expression is induced in the rat heart by cardiotrophin-1 (CT-1) [18].

Other interactions of Ctf1

• The hypertrophic effect of CT-1 was dependent on the signal transducer and activator of transcription 3 (STAT3) pathway but the hypertrophic effect of urocortin was independent of this pathway [2].
• Motoneurons retrogradely transport from the tongue radiolabeled GDNF, BDNF, and CT-1 as well as tetanus toxin [3].
• Synaptic targeting of retrogradely transported trophic factors in motoneurons: comparison of glial cell line-derived neurotrophic factor, brain-derived neurotrophic factor, and cardiotrophin-1 with tetanus toxin [3].
• In contrast, inhibition of the protective p42/p44 MAPK pathway has no effect on the hypertrophic effect of CT-1 or urocortin [2].
• By contrast, the mRNA and protein levels for CT-1 and the mRNA level for gp130 did not vary in these two models [4].

Analytical, diagnostic and therapeutic context of Ctf1

• The protein levels of IL-6, LIF and CT-1 were investigated by western blot [4].
• Following 48 h of experimental procedures, the expression of all these four molecular markers of plasticity was reduced in SD and CT1 groups compared to the CT2 and cage control groups [19].
• In vivo, CT-1 protected neonatal sciatic motoneurons against the effects of axotomy [20].
• Only CT-1 mRNA expression could be detected by Northern blot, and it increased after pressure overload [21].
• In this work we determine the activity of CT-1 in six in vitro biological assays and examine the composition of its cell surface receptor [22].

References