Disease relevance of Ctf1

• Moreover, developing embryoid bodies derived from HIF-1alpha-/- ES cells lack cardiomyogenesis, and prooxidants as well as chemical hypoxia failed to upregulate CT-1 expression [1].
• These data show that the CT-1 signaling pathway does not play a significant role in the development of cardiac hypertrophy in JVS mice [2].
• Treatment with an adenovirus encoding CT-1 efficiently protects rats against fulminant liver failure after subtotal hepatectomy, an intervention that causes 91% mortality in control animals whereas 54% of those receiving CT-1 gene therapy were long-term survivors [3].
• STAT3-TG manifested myocardial hypertrophy at 12 wk of age with increased expression of the atrial natriuretic factor (ANF), beta-myosin heavy chain (MHC), and cardiotrophin (CT)-1 genes [4].
• This augmented expression of the cardiotrophin-1 gene was not related to the severity of left ventricular hypertrophy [5].

Psychiatry related information on Ctf1

• A role for cardiotrophin-like cytokine in the circadian control of mammalian locomotor activity [6].

High impact information on Ctf1

• Overall, 40-70% of IEL from either thymus-bearing or athymic mice expressed the cytotoxic activation antigen, CT-1, and the J11d lymphocyte marker, both of which were associated with a population of Thy-1-, Lyt-2+ cytotoxic IEL [7].
• Hepatocytes cultured under serum starvation or stimulated with the pro-apoptotic cytokine transforming growth factor beta (TGF-beta) produce CT-1, which behaves as an autocrine/paracrine survival factor [3].
• In this study, we investigated the expression of CT-1 by liver cells and its possible hepatoprotective properties [3].
• RESULTS: We found that CT-1 is up-regulated during liver regeneration and exerts potent antiapoptotic effects on hepatocytic cells [3].
• Furthermore, binding of NF-IL6 (C/EBPbeta) and c-Jun to the SPRR1A promoter was observed after CT-1 stimulation [8].

Chemical compound and disease context of Ctf1

• We show that prooxidants (menadione, hydrogen peroxide) as well as chemical (CoCl2) and physiological (1% O2) hypoxia increased CT-1 as well as HIF-1alpha protein and mRNA expression in embryoid bodies, indicating that CT-1 expression is regulated by reactive oxygen species (ROS) and hypoxia [1].
• We examined whether CT-1 plays a role in the development of cardiac hypertrophy in carnitine-deficient juvenile visceral steatosis (JVS) mice [2].
• After long-term treatment with lisinopril, levels of cardiotrophin-1 mRNA were not changed, although it morphologically prevented the development of left ventricular hypertrophy [5].
• In vitro, cicaprost, an IP agonist, reduced platelet-derived growth factor-induced proliferation of wild-type noncardiomyocytes, although it could not inhibit cardiotrophin-1-induced hypertrophy of cardiomyocytes [9].

Biological context of Ctf1

• We used Lifrbeta knockout mice to assess the requirement for this receptor component in the signal transduction of CT-1 in motoneurons [10].
• Consequently, inhibition of NADPH oxidase activity by diphenylen iodonium chloride (DPI) and apocynin abolished prooxidant- and chemical hypoxia-induced upregulation of CT-1 [1].
• Basal heart rate was increased in CT-1(-/-) mice, and this difference was abolished by ganglionic block [11].
• Cardiotrophin-1 (CT-1) was identified as a growth factor for cardiac myocytes and CT-1 protects myocytes from cell death [11].
• Dobutamine stimulated similar increases in heart rate and dP/dt in both genotypes, but ventricular pressure was significantly lower in CT-1 nulls [11].

Anatomical context of Ctf1

• When added to mouse calvarial osteoblast cultures, mOSM induced secretion of IL-6 protein and elevation of mRNA whereas LIF or CT-1 did not [12].
• OSM, LIF or CT-1 also elevated the number and size of resorptive pits when cocultures were added to smooth cortical bone slices, indicating enhancement of osteoclast activity [12].
• CT-1 is highly expressed in embryonic skeletal muscle, secreted by myotubes, and promotes the survival of cultured embryonic mouse and rat MNs [13].
• Loss of leukemia inhibitory factor receptor beta or cardiotrophin-1 causes similar deficits in preganglionic sympathetic neurons and adrenal medulla [14].
• LIF deficiency leads to pronounced loss of distal axons and motor endplate alterations, whereas CNTF-and/or CT-1-deficient mice do not show significant changes in morphology of these structures [15].

Associations of Ctf1 with chemical compounds

• The signaling pathway of cardiotrophin-1 is not activated in hypertrophied ventricles of carnitine-deficient juvenile visceral steatosis (JVS) mice [2].
• The effect of CT-1 seems to be direct as it also inhibited TNF production when added to whole mouse blood cultured with lipopolysaccharide [16].
• Cardiotrophin-like cytokine labelling using Bir A biotin ligase: a sensitive tool to study receptor expression by immune and non-immune cells [17].
• The expression of CT-1, a murine CTL activation antigen, and asialo GM1, a murine NK cell marker, were variable on IEL clones, and their presence did not correlate with the changes in lytic behavior [18].

Physical interactions of Ctf1

• We did not find any difference between JVS and control mice at 2 weeks in the mRNA level of ventricular leukemia inhibitory factor (LIF) which binds to the same receptor as CT-1 [2].

Regulatory relationships of Ctf1

• Our results demonstrate that CT-1 expression in ES cells is regulated by ROS and HIF-1alpha and imply a crucial role of CT-1 in the survival and proliferation of ES-cell-derived cardiac cells [1].
• CT-1-induced astrocyte differentiation was solely gp130-dependent [19].
• In the present study, we demonstrate that treatment of embryoid bodies grown from pluripotent murine embryonic stem (ES) cells with CT-1 significantly stimulated cardiomyogenesis and increased nuclear expression of the proliferation marker Ki-67 [20].

Other interactions of Ctf1

• Mouse OSM, LIF and CT-1 strongly induced the formation of tartrate resistant acid phosphatase positive (TRAP(+)) multinucleated cells (MNC) in a dose-dependent fashion [12].
• In cntf/lif/ct-1 triple-knock-out mice, various degrees of muscle fiber type grouping are found, indicating that denervation and reinnervation had occurred [15].
• We show that LIF, CNTF, and CT-1 are synthesized in embryonic adrenal gland and spinal cord and that PSNs express LIFRbeta [14].
• CT-1 is the first bona fide muscle-derived neurotrophic factor to be identified that is required for the survival of subgroups of developing motoneurons [13].
• Regulation of cardiotrophin-1 expression in mouse embryonic stem cells by HIF-1alpha and intracellular reactive oxygen species [1].

Analytical, diagnostic and therapeutic context of Ctf1

• DEX (10(-7) M) costimulation also synergistically enhanced TRAP(+)cell numbers of LIF, and CT-1 treated cocultures [12].
• The CT-1 mRNA level was quantitatively measured by the competitive RT-PCR method [2].
• We also investigated whether CT-1 might exert protective effects in animal models of liver damage [3].
• Confocal laser microscopy of CT-1 stimulated cells reveals the assembly of sarcomeric units in series rather than in parallel, as seen after alpha-adrenergic stimulation [21].
• Similarly, Western blotting showed a twofold elevation of CT-1 protein in infected animals (P < 0.025) [22].

References