scholarly journals Sargahydroquinoic Acid Suppresses Hyperpigmentation by cAMP and ERK1/2-Mediated Downregulation of MITF in α-MSH-Stimulated B16F10 Cells

Foods ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2254
Author(s):  
Mohammed Shariful Azam ◽  
Bonggi Lee ◽  
Jae-Il Kim ◽  
Chang Geun Choi ◽  
Jinkyung Choi ◽  
...  
Keyword(s):  
Docking Simulation ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Regulatory Subunit ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Creb Activation ◽  
B16f10 Cells ◽  
Element Binding Protein ◽  
Responsive Element

Hyperpigmentation diseases of the skin require topical treatment with depigmenting agents. We investigated the hypopigmented mechanisms of sargahydroquinoic acid (SHQA) in alpha-melanocyte-stimulating hormone (α-MSH)-stimulated B16F10 cells. SHQA reduced cellular tyrosinase (TYR) activity and melanin content in a concentration-dependent manner and attenuated the expression of TYR and tyrosinase-related protein 1 (TRP1), along with their transcriptional regulator, microphthalmia-associated transcription factor (MITF). SHQA also suppressed α-MSH-induced cellular production of cyclic adenosine monophosphate (cAMP), which inhibited protein kinase A (PKA)-dependent cAMP-responsive element-binding protein (CREB) activation. Docking simulation data showed a potential binding affinity of SHQA to the regulatory subunit RIIβ of PKA, which may also adversely affect PKA and CREB activation. Moreover, SHQA activated ERK1/2 signaling in B16F10 cells, stimulating the proteasomal degradation of MITF. These data suggest that SHQA ameliorated hyperpigmentation in α-MSH-stimulated B16F10 cells by downregulating MITF via PKA inactivation and ERK1/2 phosphorylation, indicating that SHQA is a potent therapeutic agent against skin hyperpigmentation disorders.

Inhibitory action of somatostatin-14 on hormone-stimulated cyclic adenosine monophosphate induction in porcine granulosa and luteal cells

1992 ◽  
Vol 134 (2) ◽  
pp. 297-306 ◽  
Author(s):  
K. Rajkumar ◽  
D. E. Kerr ◽  
R. N. Kirkwood ◽  
B. Laarveld
Keyword(s):  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Luteal Cells ◽  
Camp Generation ◽  
Camp Induction ◽  
Camp Levels ◽  
Somatostatin 14

ABSTRACT Somatostatin-14 (SRIF-14) inhibited, in a concentration-dependent manner, LH- and forskolin-stimulated cyclic adenosine monophosphate (cAMP) induction in porcine granulosa and luteal cells. The inhibitory effect of SRIF-14 on hormone-induced cAMP generation was more potent in porcine ovarian cells than in the GH-3 pituitary cell line. The inhibitory effect of SRIF-14 was impeded by neutralizing its biological activity with specific antiserum. Preincubation of luteal and granulosa cells with phorbol 12-myristate 13-acetate (PMA) enhanced LH- and forskolin-stimulated cAMP levels. SRIF-14 failed to inhibit LH- or forskolin-stimulated cAMP levels in cells preincubated with PMA. It is concluded that SRIF-14 inhibits hormone-stimulated cAMP induction in the porcine ovary. LH-induced protein kinase C activation may be physiologically important to alleviate the inhibitory effects of SRIF-14. Journal of Endocrinology (1992) 134, 297–306

Protein kinase C activation and positive and negative agonist regulation of 3′, 5′-cyclic adenosine monophosphate levels in cultured rat Sertoli cells

1993 ◽  
Vol 128 (6) ◽  
pp. 568-572 ◽  
Author(s):  
Lars Eikvar ◽  
Kristin Austlid Taskén ◽  
Winnie Eskild ◽  
Vidar Hansson
Keyword(s):  
Sertoli Cells ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Dependent Manner ◽  
Camp Production ◽  
Camp Phosphodiesterase ◽  
Concentration Dependent Manner ◽  
Camp Formation ◽  
Pkc Activation ◽  
Stimulation Of

The present study examines the effects of 12-0-tetradecanoylphorbol-13-acetate (TPA) on agonist-regulated 3′, 5′-cyclic adenosine monophosphate (cAMP) formation and cAMP-mediated effects in cultured Sertoli cells from immature rats. Concentration-dependent stimulation of cAMP levels by follicle-stimulating hormone (FSH) was inhibited dramatically by the coaddition of 100 nmol/l TPA, which exerted a similar inhibition of glucagon- and isoproterenol-stimulated cAMP production. These results show that protein kinase C (PKC) activation by TPA attenuates Gs-protein-mediated agonist activation of cAMP production. (− )-N6(R)-Phenylisopropyladenosine (L-PIA), an A1-adenosine receptor agonist, inhibited cAMP stimulation by FSH in a concentration-dependent manner. When LPIA was added in increasing concentrations simultaneously with 100 nmol/l TPA, the L-PIA still inhibited FSH-stimulated cAMP production in a concentration-dependent manner. In the presence of TPA, the half-inhibitory concentration (IC50) for L-PIA inhibition of cAMP formation was reduced by more than one order of magnitude, indicating that PKC activation by TPA increases the sensitivity of Sertoli cells to G-protein-mediated agonist inhibition of cAMP production. The inhibitory effects of TPA on FSH-stimulated cAMP production were still observed when cAMP phosphodiesterase activity was inhibited by 1 mmol/l methylisobutylxanthine or when the activity of Gxi-protein was eliminated by pretreatment with 100 μg/l pertussis toxin. Taken together, the results indicate that PKC activation inhibits agonist-dependent stimulation of cAMP production by phosphorylation of components common to all the activating agonists used, and not via stimulation of Gi-protein activity or degradation of cAMP by cAMP phosphodiesterase activity. The increased sensitivity to L-PIA inhibition of cAMP formation induced by TPA may simply be a result of the reduced activity of the agonist-receptor/Gs-protein/C complex.

scholarly journals Therapeutic targeting of the pathological triad of extrasynaptic NMDA receptor signaling in neurodegenerations

2017 ◽  
Vol 214 (3) ◽  
pp. 569-578 ◽  
Author(s):  
Hilmar Bading
Keyword(s):  
Nmda Receptor ◽  
Nmda Receptors ◽  
Histone Deacetylases ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Cell Loss ◽  
Nuclear Accumulation ◽  
Receptor Signaling ◽  
Element Binding Protein ◽  
Responsive Element

Activation of extrasynaptic N-methyl-d-aspartate (NMDA) receptors causes neurodegeneration and cell death. The disease mechanism involves a pathological triad consisting of mitochondrial dysfunction, loss of integrity of neuronal structures and connectivity, and disruption of excitation–transcription coupling caused by CREB (cyclic adenosine monophosphate–responsive element-binding protein) shut-off and nuclear accumulation of class IIa histone deacetylases. Interdependency within the triad fuels an accelerating disease progression that culminates in failure of mitochondrial energy production and cell loss. Both acute and slowly progressive neurodegenerative conditions, including stroke, Alzheimer’s disease, amyotrophic lateral sclerosis, and Huntington’s disease, share increased death signaling by extrasynaptic NMDA receptors caused by elevated extracellular glutamate concentrations or relocalization of NMDA receptors to extrasynaptic sites. Six areas of therapeutic objectives are defined, based on which a broadly applicable combination therapy is proposed to combat the pathological triad of extrasynaptic NMDA receptor signaling that is common to many neurodegenerative diseases.

Coupling of NMDA receptors and TRPM4 guides discovery of unconventional neuroprotectants

Science ◽  
2020 ◽  
Vol 370 (6513) ◽  
pp. eaay3302 ◽  
Author(s):  
Jing Yan ◽  
C. Peter Bengtson ◽  
Bettina Buchthal ◽  
Anna M. Hagenston ◽  
Hilmar Bading
Keyword(s):  
Nmda Receptors ◽  
Small Molecules ◽  
Neuronal Loss ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Interaction Interface ◽  
Element Binding Protein ◽  
Calcium Load ◽  
Responsive Element ◽  
Intracellular Domains

Excitotoxicity induced by NMDA receptors (NMDARs) is thought to be intimately linked to high intracellular calcium load. Unexpectedly, NMDAR-mediated toxicity can be eliminated without affecting NMDAR-induced calcium signals. Instead, excitotoxicity requires physical coupling of NMDARs to TRPM4. This interaction is mediated by intracellular domains located in the near-membrane portions of the receptors. Structure-based computational drug screening using the interaction interface of TRPM4 in complex with NMDARs identified small molecules that spare NMDAR-induced calcium signaling but disrupt the NMDAR/TRPM4 complex. These interaction interface inhibitors strongly reduce NMDA-triggered toxicity and mitochondrial dysfunction, abolish cyclic adenosine monophosphate–responsive element–binding protein (CREB) shutoff, boost gene induction, and reduce neuronal loss in mouse models of stroke and retinal degeneration. Recombinant or small-molecule NMDAR/TRPM4 interface inhibitors may mitigate currently untreatable human neurodegenerative diseases.

Sign in / Sign up

Export Citation Format

Share Document