A major barrier to the commercialization of somatic embryogenesis technology in loblolly pine (Pinus taeda L.) is recalcitrance of some high-value crosses to initiate embryogenic tissue (ET) and continue early-stage somatic embryo growth. Developing initiation and multiplication media that resemble the seed environment has been shown to decrease this recalcitrance. Glutathione (GSH), glutathione disulfide (GSSG), ascorbic acid and dehydroascorbate analyses were performed weekly throughout the sequence of seed development for female gametophyte and zygotic embryo tissues to determine physiological concentrations. Major differences in stage-specific oxidation-reduction (redox) agents were observed. A simple bioassay was used to evaluate potential growth-promotion of natural and inorganic redox agents added to early-stage somatic embryo growth medium. Compounds showing statistically significant increases in early-stage embryo growth were then tested for the ability to increase initiation of loblolly pine. Low-cost reducing agents sodium dithionite and sodium thiosulfate increased ET initiation for loblolly pine and Douglas fir (Mirb) Franco. Germination medium supplementation with GSSG increased somatic embryo germination. Early-stage somatic embryos grown on medium with or without sodium thiosulfate did not differ in GSH or GSSG content, suggesting that sodium thiosulfate-mediated growth stimulation does not involve GSH or GSSG. We have developed information demonstrating that alteration of the redox environment in vitro can improve ET initiation, early-stage embryo development and somatic embryo germination in loblolly pine.
Pulsed infrared (nu approximately 2350 cm(-1)) laser excitation spectra of CO2 molecules embedded in helium droplets are reported. The spectra exhibit a sharp R(0) rovibrational line accompanied by a weak broader (deltanu approximately 10 cm(-1)) satellite band, which is shifted by 14 cm(-1) towards higher frequencies. We assign this satellite band to a simultaneous rovibrational excitation of a molecule and its helium solvation shell. The results are rationalized within a model, which includes coupling of the rotational states of a molecule and a ring of He atoms.
The interactions between the immune and nervous systems play an important role in
immune and inflammatory conditions. Substance P (SP), the unidecapeptide
RPKPQQFFGLM-NH2, is known to upregulate the production of pro-inflammatory
cytokines such as tumor necrosis factor (TNF)-α. We report here that
5-(acetylamino)-4-oxo-6-phenyl-2-hexenoic acid methyl ester (AOPHA-Me) and
4-phenyl-3-butenoic acid (PBA), two anti-inflammatory compounds developed in our
laboratory, reduce SP-stimulated TNF-α expression in RAW 264.7 macrophages. We also
show that AOPHA-Me and PBA both inhibit SP-stimulated phosphorylation of JNK and p38 MAPK.
Furthermore, molecular modeling studies indicate that both AOPHA-Me and PBA dock at the
ATP binding site of apoptosis signal-regulating kinase 1 (ASK1), a member of the MAPKs
upstream of both JNK and p38 MAPK, with predicted interaction energies of −7.0
kcal/mol and −5.9 kcal/mol, respectively; this binding overlaps with that of
staurosporine, a known inhibitor of ASK1. Taken together, these findings suggest that
AOPHA-Me and PBA inhibition of TNF-α expression in SP-stimulated RAW 264.7
macrophages is a consequence of the inhibition JNK and p38 MAPK phosphorylation. We have
previously shown that AOPHA-Me and PBA inhibit the amidative bioactivation of SP, which
also would be expected to decrease formation of pro-inflammatory cytokines. It is
conceivable that this dual action of inhibiting amidation and MAPK phosphorylation may be
of some advantage in enhancing the anti-inflammatory activity of a therapeutic
molecule.
4-Phenyl-3-butenoic acid (PBA) is an inhibitor of peptidylglycine alpha-amidating monooxygenase with anti-inflammatory properties that has been shown to inhibit the growth of ras-mutated epithelial and human lung carcinoma cells. In this report, we show that PBA also increases the acetylation levels of selected histone subtypes in a dose and time dependent manner, an effect that is attributable to the inhibition of histone deacetylase (HDAC) enzymes. Comparison studies with the known HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) using high resolution two-dimensional polyacrylamide gels and Western analysis provide evidence that PBA acts as an HDAC inhibitor within cells. PBA and a more potent amidation inhibitor, 5-(acetylamino)-4-oxo-6-phenyl-2-hexenoic acid methyl ester (AOPHA-Me), inhibit HDAC enzymes in vitro at micromolar concentrations, with IC50 values approximately 30 fold lower for AOPHA-Me than PBA for selected HDAC isoforms. Overall, these results indicate that PBA and AOPHA-Me are novel anti-tumorigenic HDAC inhibitors.
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