Chronic-alcohol exposure alters IGF1 signaling in H9c2 cells via changes in PKC delta

Ila, Richard; Solem, Michele

doi:10.1016/j.alcohol.2006.08.006

Cited by 9 publications

(7 citation statements)

References 26 publications

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“…One of these is the interaction of ER and IGF-I receptor, which has been implicated in the regulation of lordosis (54). IGF-I receptor signaling involves PKC␦ but apparently not PKC (55,56). PKC␦, is an isoform part of the novel or calcium-independent class of PKCs that appears to be upstream from PKA (57).…”

Section: Discussionmentioning

confidence: 99%

Protein Kinase C Signaling in the Hypothalamic Arcuate Nucleus Regulates Sexual Receptivity in Female Rats

et al. 2008

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Rapid membrane-mediated estradiol signaling regulating sexual receptivity requires the interaction of the estrogen receptor (ER)-alpha and the metabotropic glutamate receptor 1a (mGluR1a). A cell signaling antibody microarray revealed that estradiol activated 42 proteins in the arcuate nucleus of the hypothalamus (ARH). To begin an analysis of various signaling pathways, protein kinase A and protein kinase C (PKC)-theta, whose signaling pathways have been implicated in the estradiol regulation of sexual receptivity, were examined. In the ARH sample, the increase in phospho-protein kinase A could not be confirmed by Western blotting, in either cytosolic or membrane fractions. However, the increase in phosphorylated PKCtheta seen with the pathway array was verified by Western blotting. To study whether rapid estradiol activation of PKC regulates the ARH-medial preoptic nucleus pathway regulating lordosis, mu-opioid receptor (MOR) internalization and lordosis reflex were tested. Blocking PKC in ARH with 2-[1-(3-dimethylaminopropyl)-1H-indol-3-yl]3-(1H-indol-3-yl) maleimide significantly attenuated estradiol-induced MOR internalization. Furthermore, disruption of PKC signaling within the ARH at the time of estradiol treatment significantly diminished the lordosis reflex. Moreover, blocking PKC prevented MOR internalization when the circuit was activated by the mGluR1a agonist, (RS)-3,5-dihydroxyphenylglycine. Activation of PKC with phorbol 12, 13-dibutyrate induced MOR internalization, indicating that PKC was a critical step for membrane ERalpha-initiated mGluR1a-mediated cell signaling and phorbol 12, 13-dibutyrate significantly facilitated the lordosis reflex. Together these findings indicate that rapid membrane ERalpha-mGluR1a interactions activate PKCtheta cell signaling, which regulates female sexual receptivity.

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Section: Discussionmentioning

confidence: 99%

Protein Kinase C Signaling in the Hypothalamic Arcuate Nucleus Regulates Sexual Receptivity in Female Rats

et al. 2008

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“…Furthermore, stimulation of δ 2 ‐opioid receptors by DADLE at femtomolar to picomolar concentrations has an anti‐apoptotic effect via the mitogen‐activated protein kinase kinase (MAPK)–extracellular signal‐regulated kinase (ERK) pathway in PC12 cells deprived of serum 9 . G‐Protein‐coupled receptors (GPCR), including opioid receptors, 10,11 are known to stimulate ERK, including ERK1 and ERK2, 12,13 members of the mitogen‐activated protein kinase (MAPK) family 14–17 . Extracellular signal‐regulated kinase is required for angiotensin‐induced hypertrophy of aortic smooth muscle, as well as being critical for neuronal differentiation 18 .…”

Section: Introductionmentioning

confidence: 99%

Δ‐opioid Receptor Stimulation Enhances the Growth of Neonatal Rat Ventricular Myocytes via the Extracellular Signal‐regulated Kinase Pathway

Zhao

Wang

Yang

et al. 2007

Clin Exp Pharma Physio

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1. The aims of the present study were to determine whether delta-opioid receptor stimulation enhanced proliferation of and to investigate the role of the extracellular signal-regulated kinase (ERK) pathway in ventricular myocytes from neonatal rats. 2. At concentratins ranging from 10 nmol/L to 10 micromol/L, [D-Ala2,D-Leu5]enkephalin (DADLE) concentration-dependently promoted myocardial growth and DNA synthesis and altered the cytoskeleton. 3. At 1 micromol/L, DADLE also increased the expression and phosphorylation of ERK. 4. These effects of 1 micromol/L DADLE were abolished by 10 micromol/L naltrindole, a selective delta-opioid receptor antagonist, 10 nmol/L U0126, a selective ERK antagonist, 1 micromol/L staurosporine, an inhibitor of protein kinase (PK) C, and 100 micromol/L Rp-adenosine 3',5'-cyclic monophosphorothioate triethylammonium salt hydrate (Rp-cAMPS), an inhibitor of PKA. 5. In conclusion, delta-opioid receptor stimulation enhances the proliferation and development of the ventricular myocytes of neonatal rats. The ERK pathway and related signalling mechanisms, namely PKC and PKA, are involved.

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“…These in vivo studies differed from the in vitro results in that the ligand binding to the IGF‐IR was inhibited in this context (Cohen et al, ). Although, experimental data from multiple labs and using different cell and animal models confirmed the overall attenuation of IGF‐IR signaling pathways following chronic ethanol exposure (de la Monte et al, ; Ila and Solem, ; Cohen et al, ; Lang et al, ), the exact mechanism(s) responsible for this inhibition require further investigation.…”

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confidence: 99%

Acute Ethanol Increases IGF‐I‐Induced Phosphorylation of ERKs by Enhancing Recruitment of p52‐Shc to the Grb2/Shc Complex

Dean

Lassak

Wilk

et al. 2016

Journal Cellular Physiology

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Ethanol plays a detrimental role in the development of the brain. Multiple studies have shown that ethanol inhibits insulin-like growth factor I receptor (IGF-IR) function. Because the IGF-IR contributes to brain development by supporting neural growth, survival, and differentiation, we sought to determine the molecular mechanism(s) involved in ethanol’s effects on this membrane-associated tyrosine kinase. Using multiple neuronal cell types, we performed Western blot, immunoprecipitation, and GST-pulldowns following acute (1 – 24 hours) or chronic (3 weeks) treatment with ethanol. Surprisingly, exposure of multiple neuronal cell types to acute (up to 24 hours) ethanol (50mM) enhanced IGF-I-induced phosphorylation of ERKs, without affecting IGF-IR tyrosine phosphorylation itself, or Akt phosphorylation. This acute increase in ERKs phosphorylation was followed by the expected inhibition of the IGF-IR signaling following 3-week ethanol exposure. We then expressed a GFP-tagged IGF-IR construct in PC12 cells and used them to perform fluorescence recovery after photobleaching (FRAP) analysis. Using these fluorescently-labeled cells, we determined that 50mM ethanol decreased the half-time of the IGF-IR-associated FRAP, which implied that cell membrane-associated signaling events could be affected. Indeed, co-immunoprecipitation and GST-pulldown studies demonstrated that the acute ethanol exposure increased the recruitment of p52-Shc to the Grb2-Shc complex, which is known to engage the Ras-Raf-ERKs pathway following IGF-1 stimulation. These experiments indicate that even a short and low-dose exposure to ethanol may dysregulate function of the receptor, which plays a critical role in brain development.

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Chronic-alcohol exposure alters IGF1 signaling in H9c2 cells via changes in PKC delta

Cited by 9 publications

References 26 publications

Protein Kinase C Signaling in the Hypothalamic Arcuate Nucleus Regulates Sexual Receptivity in Female Rats

Protein Kinase C Signaling in the Hypothalamic Arcuate Nucleus Regulates Sexual Receptivity in Female Rats

Δ‐opioid Receptor Stimulation Enhances the Growth of Neonatal Rat Ventricular Myocytes via the Extracellular Signal‐regulated Kinase Pathway

Acute Ethanol Increases IGF‐I‐Induced Phosphorylation of ERKs by Enhancing Recruitment of p52‐Shc to the Grb2/Shc Complex

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