Excess tyrosine rescues the reduced activity of proliferation and differentiation of cultured recessive yellow melanocytes derived from neonatal mouse epidermis

The murine recessive yellow (Mc1r(e)) is a loss-of-function mutation in the receptor for alpha-melanocyte-stimulating hormone, melanocortin receptor 1 (Mc1r) and produces yellow coats by inducing pheomelanin synthesis in hair follicular melanocytes. However, it is not known whether the Mc1r(e) mutation affects the proliferation and differentiation of melanocytes. In this study, the proliferation and differentiation of recessive yellow epidermal melanocytes cultured in dibutyryl cyclic AMP-supplemented serum-free medium were investigated in detail. The melanocytes produced mainly eumelanin in this culture system. The proliferation of recessive yellow melanocytes was decreased compared with that of wild-type at the e-locus, black melanocytes. The differentiation of melanocytes was also delayed and inhibited in recessive yellow mice. Tyrosinase (TYR) activity and TYR-related protein 1 (TRP1) and TRP2 (dopachrome tautomerase, DCT) expressions were decreased and, in addition, the maturation of stage IV melanosomes was inhibited. Excess l-tyrosine (l-Tyr) added to the culture media rescued the reduced activity of proliferation of melanocytes. l-Tyr also stimulated TYR activity and TRP1 and TRP2 expressions as well as the maturation of stage IV melanosomes and pigmentation. These results suggest that the Mc1r(e) mutation affects the proliferation and differentiation of melanocytes and l-Tyr rescues the reduced proliferative and differentiative activities by stimulating TYR activity and TRP1 and TRP2 expressions as well as melanosome maturation.     

Intensity enhancement of intraligand singlet-triplet π-π transition for the coordinated β-diketonate in Ni(II) complexes with a nitroxide radical

Room temperature and low temperature magnetic circular dichroism (MCD) in the intraligand spin-forbidden singlet-triplet π-π^∗ transition for the coordinated β-diketonate ligands were observed for the β-diketonato Ni(II) complexes with a chelated imino or nitronyl nitroxide radical, but not for the β-diketonato Ni(II) complexes without the radical ligands. This is elucidated by the borrowing mechanism from the singlet-singlet π-π^∗ transition through the hypothetical interligand β-diketonate-to-radical charge transfer (LLCT) in contrast to the case of Cr(III) complexes.     

Mycophenolic acid as a latent agonist of PPARgamma

Mycophenolic acid (MPA), known as an inhibitor of inosine monophosphate dehydrogenase (IMPDH), was found to inhibit the differentiation of 3T3-L1 pre-adipocytes into mature adipocytes. Although the effect of MPA was attributed to inhibition of IMPDH, we uncovered a hidden biological property of MPA as an agonist of peroxisome proliferator activated receptor gamma (PPARgamma).     

Antitumor studies. Part 1: design, synthesis, antitumor activity, and AutoDock study of 2-deoxo-2-phenyl-5-deazaflavins and 2-deoxo-2-phenylflavin-5-oxides as a new class of antitumor agents

Novel 2-deoxo-2-phenyl-5-deazaflavins and 2-deoxo-2-phenylflavin-5-oxides were prepared as a new class of antitumor agents and showed significant antitumor activities against NCI-H 460, HCT 116, A 431, CCRF-HSB-2, andKB cell lines. In vivo investigation, 2-deoxo-10-methyl-2-phenyl-5-deazaflavin exhibited the effective antitumor activity against A 431 human adenocarcinoma cells transplanted subcutaneously into nude mouse. Furthermore, AutoDock study has been done by binding of the flavin analogs into PTK pp60(c-src), where a good correlation between their IC(50) and AutoDock binding free energy was exhibited. In particular, 2-deoxo-2-phenylflavin-5-oxides exhibited the highest potential binding affinity within the binding pocket of PTK.     

Novel sequence-responding fluorescent oligoDNA probe bearing a silylated pyrene molecule

A novel fluorescent phosphoramidite derivative of dimethylsilylated pyrene was prepared and incorporated into oligoDNA. The fluorescent oligoDNA exhibited marked fluorescent signal upon binding to the fully matched complementary DNA strand, however, the signal was strongly quenched in the single-stranded form as well as in the duplex having mismatched base pair at the terminus of the duplex-forming region.     

Repeated-batch fermentation of lignocellulosic hydrolysate to ethanol using a hybrid Saccharomyces cerevisiae strain metabolically engineered for tolerance to acetic and formic acids

A major challenge associated with the fermentation of lignocellulose-derived hydrolysates is improved ethanol production in the presence of fermentation inhibitors, such as acetic and formic acids. Enhancement of transaldolase (TAL) and formate dehydrogenase (FDH) activities through metabolic engineering successfully conferred resistance to weak acids in a recombinant xylose-fermenting Saccharomyces cerevisiae strain. Moreover, hybridization of the metabolically engineered yeast strain improved ethanol production from xylose in the presence of both 30 mM acetate and 20 mM formate. Batch fermentation of lignocellulosic hydrolysate containing a mixture of glucose, fructose and xylose as carbon sources, as well as the fermentation inhibitors, acetate and formate, was performed for five cycles without any loss of fermentation capacity. Long-term stability of ethanol production in the fermentation phase was not only attributed to the coexpression of TAL and FDH genes, but also the hybridization of haploid strains.     

Production of novel antioxidative prenyl naphthalen-ols by combinational bioconversion with dioxygenase PhnA1A2A3A4 and prenyltransferase NphB or SCO7190

We performed combinational bioconversion of substituted naphthalenes with PhnA1A2A3A4 (an aromatic dihydroxylating dioxygenase from marine bacterium Cycloclasticus sp. strain A5) and prenyltransferase NphB (geranyltransferase from Streptomyces sp. strain CL190) or SCO7190 (dimethylallyltransferase from Streptomyces coelicolor A3(2)) to produce prenyl naphthalen-ols. Using 2-methylnaphthalene, 1-methoxynaphthalene, and 1-ethoxynaphthalene as the starting substrates, 10 novel prenyl naphthalen-ols were produced by combinational bioconversion. These novel prenyl naphthalen-ols each showed potent antioxidative activity against a rat brain homogenate model. 2-(2,3-Dihydroxyphenyl)-5,7-dihydroxy-chromen-4-one (2',3'-dihydroxychrysin) generated with another aromatic dihydroxylating dioxygenase and subsequent dehydrogenase was also geranylated at the C-5'-carbon by the action of NphB.