Cholinergic differentiation factor (CDF/LIF) promotes survival of isolated rat embryonic motoneurons in vitro

Martinou, Jean‐Claude; Martinou, Isabelle; Kato, Ann C.

doi:10.1016/0896-6273(92)90094-t

Cited by 247 publications

(152 citation statements)

References 55 publications

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“…Thus, LIF, interleukin-6, and oncostatin-M deserve a thorough evaluation as additional potential neurotrophic molecules for motoneurons. Indeed, in vitro and in vivo effects of LIF on motoneurons have been observed (34,39,58). However, the physiological relevance of these observations remains to be established, particularly in view of the fact that a first evaluation of LIF -/-mice did not show any changes in spinal motoneurons either at the morphological or functional levels (84).…”

Section: Thoenen Hughes and Sendtnermentioning

confidence: 99%

“…Progress was predominantly determined by an improvement of the motoneuron cell culture procedures (3,10,12,33,34,39) and the identification of neurotrophic molecules in adult and/or embryonic skeletal muscles with already known neurotrophic actions on other populations of neurons in vitro and in vivo (3,13,34,36,38,39,45,54,58,80). The importance of appropriate culture systems for motoneurons is demonstrated by the fact that, for a long time, no single, defined molecule could be demonstrated to have a convincing trophic action on motoneurons.…”

Section: Introductionmentioning

confidence: 99%

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Trophic Support of Motoneurons: Physiological, Pathophysiological, and Therapeutic Implications

Thoenen¹,

Hughes²,

Sendtner³

1993

Experimental Neurology

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Section: Thoenen Hughes and Sendtnermentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Trophic Support of Motoneurons: Physiological, Pathophysiological, and Therapeutic Implications

Thoenen¹,

Hughes²,

Sendtner³

1993

Experimental Neurology

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“…In neuronal cell types, a number of peripherally derived neurotrophic factors have been shown to play a vital role in the regulation of the survival of spinal motoneurons at a variety of stages of development (21). In this regard, two members of the IL-6 family of cytokines, LIF and CNTF, have been shown to play an important role in maintaining the viability of motoneurons in long- term culture and also in the in vivo context (21)(22)(23)(24)(25). Interestingly, mice that harbor a targeted disruption of the ␣ subunit of the CNTF receptor or the ␤ receptor of the LIF receptor die shortly after birth and display a severe loss of more than 48% of the motoneurons in the spinal cord and brain stem (26,27).…”

Section: Ct-1-dependent Pathways Promote Myocardial Cell Survival Viamentioning

confidence: 99%

Cardiotrophin 1 (CT-1) Inhibition of Cardiac Myocyte Apoptosis via a Mitogen-activated Protein Kinase-dependent Pathway

Sheng¹,

Knowlton

Chen³

et al. 1997

Journal of Biological Chemistry

377

212

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Cardiac muscle cell survival plays a critical role in maintaining the normal function of the heart and possibly in cardiac development. Adult cardiac muscle cells are terminally differentiated and therefore have lost their proliferative capacity. In contrast to skeletal muscle, the myocardium does not contain satellite heart muscle cells, and irreversible heart injury results in scarring and an eventual decrease in global cardiac function. In response to mechanical stimuli and hemodynamic stress, the adult myocardium activates an adaptive hypertrophic response that is characterized by an increase in myocardial cell size without a concomitant increase in myocyte number (For review, see Refs. 1 and 2). However, during longstanding exposure to hypertension or other forms of hemodynamic stress, a distinct form of myocardial cell hypertrophy can be activated in which the heart becomes dilated and individual cardiac myocytes exhibit an increase in cell length, reflecting the addition of new sarcomeric units in series (3,4). This dilatation of the heart is usually accompanied by fibrosis, microscarring, and the loss of viable cardiac myocytes throughout the myocardium. As a result of cardiac dilatation and myocyte dropout, the myocardium ultimately develops an irreversible loss of function and ensuing cardiac muscle failure (4). As such, the identification of the signaling pathways that mediate distinct forms of cardiac muscle cell hypertrophy, dysfunction, and cardiac muscle cell survival are critical to the ultimate elucidation of the molecular basis of cardiac muscle failure.By coupling expression cloning with an embryonic stem cellbased model of in vitro cardiogenesis (5), recent studies have identified cardiotrophin 1 (CT-1), 1 a novel cardiac cytokine that was isolated in a search for new factors that induce cardiac myocyte hypertrophy (5). CT-1 is a new member of the IL-6 family of cytokines that exert their biological effects through the shared signaling subunit gp130 (3, 5-7) and can activate a distinct form of myocardial cell hypertrophy that is characteristic of volume overload cardiac hypertrophy at the molecular, morphological, and cellular levels (3). Importantly, cardiotrophin 1 has been shown to be capable of promoting survival of both embryonic and neonatal rat ventricular muscle cells (8). Recent studies have demonstrated that CT-1 exerts its effects on cardiac muscle cell hypertrophy through promoting the heterodimerization of gp130 with the leukemia inhibitory factor

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“…CNTF mediates cell survival in several different neuronal populations including motor and sensory neurons (1)(2)(3)(4), induces reactive gliosis (5), and may stimulate differentiation of precursors toward the astrocytic lineage (4,6,7). CNTF also initiates an adrenergicto-cholinergic switch in the neurotransmitter phenotype of primary sympathetic neurons (3, 8 -11).…”

mentioning

confidence: 99%

Identification of a Novel gp130-responsive Site in the Vasoactive Intestinal Peptide Cytokine Response Element

Jones

Conover

Symes

2000

Journal of Biological Chemistry

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The neuropoietic cytokine ciliary neurotrophic factor (CNTF) potently induces transcription of the vasoactive intestinal peptide (VIP) gene through a 180-base pair (bp) cytokine response element (CyRE) in the VIP promoter. We have previously shown that CNTF induction of STAT and AP-1 protein binding within the CyRE is necessary to mediate CNTF induction of VIP gene transcription. We now show that a third, previously uncharacterized site at the 3-end of the CyRE is also critical to CNTF induction of CyRE transcription. A 4-bp mutation in this 3-region reduced CNTF-mediated induction of transcription ϳ80%. Whereas mutations in both the STAT and AP-1 sites substantially reduced CNTF induction of transcription, mutations in these sites together with the novel 3-site completely abolished the ability of CNTF to induce CyRE-mediated transcription. Gel shift analysis indicated that a complex in neuroblastoma cells bound specifically to this 3-site. This complex was not altered by CNTF treatment. Mutations in an 8-bp sequence (TTACTGGA) eliminated binding of this protein complex and markedly reduced transcriptional activation of the CyRE by CNTF. Thus, we have identified a protein complex binding to a novel DNA sequence that is necessary for full CNTF induction of VIP gene transcription.Ciliary neurotrophic factor (CNTF), 1 a gp130 cytokine with neurotrophic activity, performs many functions in the central and peripheral nervous systems. CNTF mediates cell survival in several different neuronal populations including motor and sensory neurons (1-4), induces reactive gliosis (5), and may stimulate differentiation of precursors toward the astrocytic lineage (4, 6, 7). CNTF also initiates an adrenergicto-cholinergic switch in the neurotransmitter phenotype of primary sympathetic neurons (3, 8 -11). As part of this phenotypic switch, CNTF induces the expression of various neuropeptide genes including vasoactive intestinal peptide (VIP) (9, 10, 12). To identify the molecular mechanisms by which the gp130 cytokines regulate gene transcription in the nervous system, we have examined CNTF induction of VIP gene expression.All the gp130 cytokines (interleukin-6, leukemia inhibitory factor (LIF), oncostatin M, cardiotrophin-1, and interleukin-11) activate similar intracellular signaling pathways (13-16) by virtue of shared components of their receptor complex. CNTF binding to CNTF receptor-␣, a glycosyl-phosphatidylinositollinked subunit, leads to association of CNTF receptor-␣ with LIF receptor-␤ and then with gp130 to form a trimeric or hexameric receptor complex (14,(17)(18)(19). LIF also signals through LIF receptor-␤ and gp130, but does not require CNTF receptor-␣. LIF and CNTF share the transmembrane subunits gp130 and LIF receptor-␤ and thus have similar intracellular signal transduction mechanisms. Various signaling moieties are activated by the gp130 cytokines, including members of the JAK/STAT pathway (20 -22); the Ras/MAPK pathway (13, 23-25); SHP-2 tyrosine phosphatase (26); protein phosphatase 2A (27); Src, protein kina...

show abstract

Cholinergic differentiation factor (CDF/LIF) promotes survival of isolated rat embryonic motoneurons in vitro

Cited by 247 publications

References 55 publications

Trophic Support of Motoneurons: Physiological, Pathophysiological, and Therapeutic Implications

Trophic Support of Motoneurons: Physiological, Pathophysiological, and Therapeutic Implications

Cardiotrophin 1 (CT-1) Inhibition of Cardiac Myocyte Apoptosis via a Mitogen-activated Protein Kinase-dependent Pathway

Identification of a Novel gp130-responsive Site in the Vasoactive Intestinal Peptide Cytokine Response Element

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