ABSTRACT
In the present in vitro study, the involvement of cAMP dependent-protein kinase A (PKA) and calcium-dependent protein kinase C (PKC) in the regulation of forebrain (telencephalon and hypothalamus) tyrosine hydroxylase (TH) activity was demonstrated during the reproductive seasons of the female catfish H. fossilis. In the concentration studies conducted in prespawning phase, cAMP (0.05 nM, 0.5 nM, 1 mM and 2.0 mM) or the phosphodiesterase inhibitor isobutylmethylxanthine (IBMX-0.5-2.0 mM) stimulated enzyme activity. Likewise, the incubation of the enzyme preparations with the cAMP dependent-protein kinase A inhibitor H-89 (1 and 10 microM) and PKC inhibitor calphostin C (cal C; 1 and 10 microM) inhibited enzyme activity in a concentration-dependent manner. In seasonal studies, the incubation of the enzyme preparations with cAMP (1 mM), IBMX (1 mM), H-89 (10 microM) and cal-C (10 microM) produced season-dependent effects on enzyme activity. The stimulatory effect of cAMP and IBMX and the inhibitory effect of H-89 and cal C were greater in the resting and spawning phases. The results suggest the involvement of both signal transduction pathways in TH activation vis-à-vis catecholaminergic activity with a more dominant role by the cAMP-PKA pathway.
Subject(s)
1-Methyl-3-isobutylxanthine/pharmacology , Animals , Brain/enzymology , Calcium/metabolism , Catfishes , Cyclic AMP/metabolism , Cyclic AMP-Dependent Protein Kinases/metabolism , Female , Fossils , Isoquinolines/pharmacology , Naphthalenes/pharmacology , Protein Kinase C/metabolism , Seasons , Signal Transduction , Sulfonamides/pharmacology , Tyrosine 3-Monooxygenase/chemistryABSTRACT
Xanthohumol (XH), the principal prenylflavonoid of the hop plant (Humulus lupulus L.), dose-dependently inhibited isobutylmethylxanthine (IBMX)-induced melanogenesis in B16 melanoma cells, with little cytotoxicity at the effective concentrations. Decreased melanin content was accompanied by reduced tyrosinase enzyme activity, protein and mRNA expression. The levels of tyrosinase-related protein 1 and 2 mRNAs were decreased by XH. XH also inhibited alpha-melanocyte stimulating hormone- or forskolin-induced increases in melanogenesis, suggesting an action on the cAMP-dependent melanogenic pathway. XH downregulated the protein and mRNA expression of microphthalmia-associated transcription factor (MITF), a master transcriptional regulator of key melanogenic enzymes. These results suggest that XH might act as a hypo-pigmenting agent through the downregulation of MITF in the cAMP-dependent melanogenic pathway.
Subject(s)
Animals , Mice , 1-Methyl-3-isobutylxanthine/pharmacology , Cell Line , Cell Survival/drug effects , Dose-Response Relationship, Drug , Down-Regulation , Drug Antagonism , Colforsin/pharmacology , Humulus , Intramolecular Oxidoreductases/antagonists & inhibitors , Melanins/antagonists & inhibitors , Melanocytes/drug effects , Melanoma, Experimental , Membrane Glycoproteins/antagonists & inhibitors , Microphthalmia-Associated Transcription Factor/antagonists & inhibitors , Monophenol Monooxygenase/antagonists & inhibitors , Oxidoreductases/antagonists & inhibitors , Propiophenones/pharmacology , Signal Transduction/drug effects , alpha-MSH/metabolismABSTRACT
No abstract available.