Juxtanodin (JN, also known as ermin) was initially identified as an actin cytoskeleton-related oligodendroglial protein in the rat central nervous system. It was subsequently also found in the rat olfactory neuroepithelium, especially at the apical junctional belt of the sustentacular cells. We further examined JN expression and functional roles in the retina using fluorescence histochemistry, confocal microscopy, immuno-electron microscopy, molecular biology, and cell culture. Prominent JN expression was found in the photoreceptor-supporting retinal pigment epithelium (RPE), especially in a zone corresponding to the apices of RPE cells, at the roots of the RPE microvilli, and at the base of RPE cells next to the Bruch's membrane. Partial co-localization of JN immunoreactivity with F-actin (labeled with phalloidin) was observed at the apices and bases of RPE cells. No JN was detected in other cell types of the retina. In cultured human RPE cell line ARPE-19, expression of extrinsic JN up-regulated formation of actin cytoskeleton stress fibers, caused redistribution of more F-actin fibers to the cell periphery, and promoted spreading/enlargement of transfected cells. These findings suggest possible roles of JN in RPE molecular transport, phagocytosis and formation of outer blood-retinal barrier, or possible involvement of JN expression perturbations in pathogenesis of such retinal disorders as proliferative vitreoretinopathy and age-related macular degeneration.
Acetohydroxy acid synthase (AHAS) is one of several enzymes that require thiamine diphosphate and a divalent cation as essential cofactors. Recently, the three-dimensional structure of the enzyme from yeast has been determined [Pang et al., J. Mol. Biol. 317 (2002) 249-262]. While this structure sheds light on the binding of the cofactors and the reaction mechanism, the interactions between the substrates and the enzyme remain unclear. We have studied the pH dependence of kinetic parameters in order to obtain information about the chemical mechanism in the active site. Data are consistent with a mechanism in which substrate selectively catalyzed to the enzyme with an unprotonated base having a pK of 6.48, and a protonated group having a pK of 8.25 for catalysis. The temperature dependence of kinetic parameters was pH-dependent, and the enthalpies of ionization, DeltaH(ion), calculated from the slope of pK(1) and pK(2) are both pH-independent. The solvent perturbation of kinetic parameters was pH-dependent, and the pK(1) from the acidic side and the pK(2) from the basic side were shifted down 0.4 pH units and shifted up 0.6 units as water was replaced by 15% ethanol, respectively. The data are discussed in terms of the acid-base chemical mechanism.
Adipogenesis is the process of adipocyte differentiation which increases lipid accumulation and ROS production. Many studies revealed that obesity is caused by excessive lipid accumulation and it leads metabolic diseases. Also, ROS production by oxidative stress induced insulin resistance which accompanies obesity and is a risk factor of type 2 diabetes. Ginsenoside Rg1 is one of the major components in panaxa ginseng, as a class of steroid glycosides, and triterpene saponins. Our result showed that Rg1 decreased lipid accumulation, C/EBPα, PPARγ, aP2 mRNA expression, C/EBPα, PPARγ protein expression and ROS production in a dose‐dependent manner. In addition, protein expression of early aipogenic factor C/EBPβ which induces C/EBPα, PPARγ was reduced during early adipogenesis. Our data suggests that Ginsenoside Rg1 inhibits lipid accumulation and ROS generation during early adipocyte differentiation. Depend on these data, we are planning to investigate anti‐oxidative factors.
To find a new type of cholinergic drug, phosphonamidate compounds 18-32 were synthesized using a click reaction between propargylated-9,10-Dihydro-9-oxa-10-phosphaphenanthrene-10-oxide (DOPO, 2) and substituted benzyl azide. Their inhibitory activity against butyrylcholinesterase (BuChE) and acetylcholinesterase (AChE) was evaluated. Compound 31 was the most active of the 15 compounds (IC 50 = 3.14 AE 0.02 μM for equine BuChE), whose IC 50 value was slightly lower than the IC 50 value of galantamine (IC 50 = 9.4 AE 2.50 for equine BuChE).
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