Nucleotide sequence of the gene encoding the Corynebacterium glutamicum mannose enzyme II and analyses of the deduced protein sequence

Abstract The complete nucleotide sequence of the gene encoding the Corynebacterium glutamicum mannose enzyme II (EII^Man) was determined. The gene consisted of 2052 base pairs encoding a protein of 683 amino acid residues; the molecular mass of the protein subunit was calculated to be 72570 Da. The N-terminal hydrophilic domain of EII^Man showed 39.7% homology with a C-terminal hydrophilic domain of Escherichia coli glucose-specific enzyme II (EII^Glc). Similar homology was shown between the C-terminal sequence of EII^Man and the E. coli glucose-specific enzyme III (EIII^Glc), or the EIII-like domain of Streptococcus mutans sucrose-specific enzyme II. Sequence comparison with other EIIs showed that EII^Man contained residues His-602 and Cys-28 which were homologous to the potential phosphorylation sites of EIII^Glc, or EIII-like domains, and hydrophilic domains (IIB) of several EIIs, respectively.     

Neurodegenerative lysosomal disorders: a continuum from development to late age

Neuronal survival requires continuous lysosomal turnover of cellular constituents delivered by autophagy and endocytosis. Primary lysosomal dysfunction in inherited congenital "lysosomal storage" disorders is well known to cause severe neurodegenerative phenotypes associated with accumulations of lysosomes and autophagic vacuoles (AVs). Recently, the number of inherited adult-onset neurodegenerative diseases caused by proteins that regulate protein sorting and degradation within the endocytic and autophagic pathways has grown considerably. In this Perspective, we classify a group of neurodegenerative diseases across the lifespan as disorders of lysosomal function, which feature extensive autophagic-endocytic-lysosomal neuropathology and may share mechanisms of neurodegeneration related to degradative failure and lysosomal destabilization. We highlight Alzheimer's disease as a disease within this group and discuss how each of the genes and other risk factors promoting this disease contribute to progressive lysosomal dysfunction and neuronal cell death.     

Synthesis of [1'-fluoro-2',2'-bis-(hydroxymethyl)cyclopropylmethyl]purines as antiviral agents

[1'-Fluoro-2',2'-bis-(hydroxymethyl)cyclopropylmethyl]purines were designed, synthesized and their antiviral activity against poliovirus, HSV and HIV was evaluated.     

Comparisons of the NACP Self-Oligomerizations Induced by Aβ25-35 in the Presence of Dicyclohexylcarbodiimide and N-(Ethoxycarbonyl)-2-Ethoxy-1,2-Dihydroquinoline

NACP, the precursor protein of the non-amyloid /A4 protein (A) component of Alzheimer's disease (AD) amyloid, also known as -synuclein was shown to undergo self-oligomerization only in the presence of a modified A fragment (residues 25–35) by using a relatively hydrophobic coupling reagent, dicyclohexylcarbodiimide (DCCD). Since the oligomerization not only required a relatively high concentration of DCCD but also its efficiency was suppressed even at a slightly basic pH of 7.5, another coupling reagent called N-(ethoxycarbonyl)-2-ethoxy-1,2-dihydroquinoline (EEDQ) was examined in order to make use of this technique to access the functional aspects of NACP in vitro by exploring more accurate and reproducible reaction conditions. The EEDQ also gave rise to the NACP oligomerization only in the presence of A25-35 among the variously modified A peptides. The reagent was about three times more effective than DCCD in terms of its optimal concentration to visualize the oligomers. In addition, its oligomerizing potency was not affected by the basic condition. Although physiological and pathological significance of the NACP self-oligomerization are currently unknown, this dramatic phenomenon and its visualization technique could shed light on the determination of molecular relationships of NACP with various intracellular or extracellular biomolecules related to the pathological conditions of Alzheimer's and Parkinson's diseases.     

Macroautophagy--a novel Beta-amyloid peptide-generating pathway activated in Alzheimer's disease

Macroautophagy, which is a lysosomal pathway for the turnover of organelles and long-lived proteins, is a key determinant of cell survival and longevity. In this study, we show that neuronal macroautophagy is induced early in Alzheimer's disease (AD) and before beta-amyloid (Abeta) deposits extracellularly in the presenilin (PS) 1/Abeta precursor protein (APP) mouse model of beta-amyloidosis. Subsequently, autophagosomes and late autophagic vacuoles (AVs) accumulate markedly in dystrophic dendrites, implying an impaired maturation of AVs to lysosomes. Immunolabeling identifies AVs in the brain as a major reservoir of intracellular Abeta. Purified AVs contain APP and beta-cleaved APP and are highly enriched in PS1, nicastrin, and PS-dependent gamma-secretase activity. Inducing or inhibiting macroautophagy in neuronal and nonneuronal cells by modulating mammalian target of rapamycin kinase elicits parallel changes in AV proliferation and Abeta production. Our results, therefore, link beta-amyloidogenic and cell survival pathways through macroautophagy, which is activated and is abnormal in AD.     

Ethylparaben induces apoptotic cell death in human placenta BeWo cells via the Caspase-3 pathway

ABSTRACT

Parabens are generally used as preservatives in foods, pharmaceuticals, and various other commercial products. Among them, ethylparaben has weaker estrogenic characteristics than endogenous estrogen. However, growing evidence indicates that ethylparaben has an adverse effect on various human tissues. Here, we investigated whether ethylparaben induces cell death by affecting cell viability, cell proliferation, cell cycle, and apoptosis using the human placenta cell line BeWo. Ethylparaben significantly decreased cell viability in a dose-dependent manner. It caused cell cycle arrest at sub-G1 by reducing the expression of cyclin D1, whereas it decreased the cell proportion at the G0/G1 and S phases. Furthermore, we verified that ethylparaben induces apoptotic cell death by enhancing the activity of Caspase-3. Taken together, our results suggest that ethylparaben exerts cytotoxic effects in human placental BeWo cells via cell cycle arrest and apoptotic pathways.