Melatonin activates PKC-α but not PKC-ε in N1E-115 cells

Benítez‐King, Gloria; Hernández, Marı́a Eugenia; Tovar, Rosalinda; Ramı́rez, Gerardo

doi:10.1016/s0197-0186(01)00021-3

Cited by 48 publications

(37 citation statements)

References 36 publications

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“…Therefore, we examined whether the Asp 294 -to-glycine mutation in PKCa would result in communication breakdowns between cells with this mutation and extracellular antitumorigenic signals using a cellular model of melatonin-induced neurite outgrowth. Consistent with previous findings (19), we found that the neurite outgrowth in N1E-115 was augmented by the wild-type PKCa (P < 0.001 compared with empty vector; Fig. 4A and B).…”

Section: Resultssupporting

confidence: 92%

“…At physiological concentrations, melatonin can inhibit cancer cell proliferation and reduce metastasic capacity, whereas at pharmacological concentrations, melatonin exhibits cytotoxic activities and induces apoptosis (17). In neuronal cells, melatonin activates PKCa via the ERK pathway (18) and elicits the translocation of PKCa to membranes as well as induction of differentiation in the form of neurite outgrowth (19). Therefore, we examined whether the Asp 294 -to-glycine mutation in PKCa would result in communication breakdowns between cells with this mutation and extracellular antitumorigenic signals using a cellular model of melatonin-induced neurite outgrowth.…”

Section: Resultsmentioning

confidence: 99%

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The PKCα-D294G Mutant Found in Pituitary and Thyroid Tumors Fails to Transduce Extracellular Signals

Zhu

Dong²,

Tan³

et al. 2005

Cancer Research

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Protein kinase C (PKC) is a key regulator of cell proliferation, differentiation, and apoptosis and is one of the drug targets of anticancer therapy. Recently, a single point mutation (D294G) in PKCA has been found in pituitary and thyroid tumors with more invasive phenotype. Although the PKCA-D294G mutant is implicated in the progression of endocrine tumors, no apparent biochemical/cell biological abnormalities underlying tumorigenesis with this mutant have been found. We report here that the PKCA-D294G mutant is unable to bind to cellular membranes tightly despite the fact that it translocates to the membrane as efficiently as the wild-type PKCA upon treatment of phorbol ester. The impaired membrane binding is associated with this mutant's inability to transduce several antitumorigenic signals as it fails to mediate phorbol ester-stimulated translocation of myristoylated alanine-rich protein kinase C substrate (MARCKS), to activate mitogen-activated protein kinase and to augment melatonin-stimulated neurite outgrowth. Thus, the PKCA-D294G is a loss-of-function mutation. We propose that the wild-type PKCA may play important antitumorigenic roles in the progression of endocrine tumors. Therefore, developing selective activators instead of inhibitors of PKCA might provide effective pharmacological interventions for the treatment of certain endocrine tumors. (Cancer Res 2005; 65(11): 4520-4)

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Section: Resultssupporting

confidence: 92%

Section: Resultsmentioning

confidence: 99%

The PKCα-D294G Mutant Found in Pituitary and Thyroid Tumors Fails to Transduce Extracellular Signals

Zhu

Dong²,

Tan³

et al. 2005

Cancer Research

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“…Four mechanisms have been described for the action of melatonin: (i) interaction with membrane receptors [8], (ii) binding to nuclear receptors [9], (iii) in-* Corresponding author. teraction with cytoplasmic proteins [10], and (iv) antioxidant activity, including scavenging properties [11]. A functional relationship between the pineal gland and immune system in different mammalian species has been supported by many experimental findings [7,12].…”

mentioning

confidence: 92%

Expression of membrane and nuclear melatonin receptor mRNA and protein in the mouse immune system

Carrillo-Vico

Garcı́a-Pergañeda²,

Naji

et al. 2003

Cellular and Molecular Life Sciences (CMLS)

124

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The neurohormone melatonin plays a fundamental role in neuroimmunomodulation of several mammalian species, including mice. This effect is supported by the existence of specific melatonin-binding sites in murine immunocompetent organs. Moreover, using melatonin receptor analogues, several effects of the neurohormone on mice physiology through its membrane and nuclear receptors have been described. The expression of these receptors has never been studied, despite indirect evidence showing the presence of melatonin receptor in the murine immune system. At present, the MT1 and MT2 membrane receptors, and nuclear receptors belonging to the RZR/ROR family have been related to the immunomodulator effect of melatonin. Here, we show the presence of membrane and nuclear melatonin-binding sites in mouse thymus and spleen, using the specific melatonin membrane (S 20098) and nuclear (CGP 52608) receptor agonist. To confirm the presence of melatonin receptors, we analyzed the presence of membrane and nuclear receptor mRNA and protein by RT-PCR, Southern blot, and Western blot. Thus, we show that MT1 and RORalpha receptor mRNA and protein are expressed in both thymus and spleen, while MT2 receptor mRNA is only detected in the thymus. This expression of melatonin receptors strongly supports the idea of an immunomodulatory role of melatonin through its receptors.

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“…Melatonin has pleiotropic neurobiological actions mediated through cell membrane receptors (Dubocovich, 2007;Dubocovich et al, 2005) and by intracellular signaling cascades (Benitez-King et al, 2001;Benitez-King et al, 1993;Soto-Vega et al, 2004). In addition, melatonin might scavenge free oxygen radicals and thereby act neuroprotective (Reiter, 1998a(Reiter, , 1998b.…”

Section: Introductionmentioning

confidence: 99%

Melatonin Modulates Cell Survival of New Neurons in the Hippocampus of Adult Mice

Ramírez-Rodríguez

Klempin

Babu

et al. 2009

Neuropsychopharmacol

196

170

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Regulation of adult hippocampal neurogenesis is influenced by circadian rhythm, affected by the manipulation of sleep, and is disturbed in animal models of affective disorders. These observations and the link between dysregulation of the circadian production of melatonin and neuropsychiatric disorders prompted us to investigate the potential role of melatonin in controlling adult hippocampal neurogenesis. In vitro, melatonin increased the number of new neurons derived from adult hippocampal neural precursor cells in vitro by promoting cell survival. This effect was partially dependent on the activation of melatonin receptors as it could be blocked by the application of receptor antagonist luzindole. There was no effect of melatonin on cell proliferation. Similarly, in the dentate gyrus of adult C57BL/6 mice in vivo, exogenous melatonin (8 mg/kg) also increased the survival of neuronal progenitor cells and post-mitotic immature neurons. Melatonin did not affect precursor cell proliferation in vivo and also did not influence neuronal and glial cell maturation. Moreover, melatonin showed antidepressant-like effects in the Porsolt forced swim test. These results indicate that melatonin through its receptor can modulate the survival of newborn neurons in the adult hippocampus, making it the first known exogenously applicable substance with such specificity

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Melatonin activates PKC-α but not PKC-ε in N1E-115 cells

Cited by 48 publications

References 36 publications

The PKCα-D294G Mutant Found in Pituitary and Thyroid Tumors Fails to Transduce Extracellular Signals

The PKCα-D294G Mutant Found in Pituitary and Thyroid Tumors Fails to Transduce Extracellular Signals

Expression of membrane and nuclear melatonin receptor mRNA and protein in the mouse immune system

Melatonin Modulates Cell Survival of New Neurons in the Hippocampus of Adult Mice

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