Acetone-regulated synthesis and degradation of cytochrome P450E1 and cytochrome P4502B1 in rat liver [corrected

The regulation of CYP2E1 and 2B1 was studied by following mRNA levels, catalytic activities and the subcellular distribution of the apoproteins in rat liver 0, 6, 12, 24, 48 and 96 h after a single intragastric dose of acetone. No changes were observed in hepatic CYP2E1 mRNA levels at any time after acetone treatment, whereas rapid rises were observed in the microsomal amount of CYP2E1 protein and CYP2E1-catalyzed 4-nitrophenol hydroxylase and carbon-tetrachloride-initiated lipid-peroxidation activities. However, CYP2E1-dependent catalytic activities declined much faster than the immunodetectable CYP2E1 protein, suggesting that this cytochrome P-450 is inactivated prior to degradation. Similar results were seen in primary hepatocyte cultures. By contrast, concomitant changes in levels of CYP2B1 and CYP2B1-dependent O-depentylation of pentoxyresorufin were observed in the same microsomal preparations. Investigation of the degradative mechanism of both CYP2E1 and CYP2B1 by immunoquantitation of the proteins in lysosomes and by immunohistochemistry indicated their degradation via an autophagic-lysosomal pathway. The data suggest that CYP2E1 is acutely inactivated in the endoplasmic reticulum and that degradation of this isozyme occurs, at least in part, by the lysosomal route. By contrast, CYP2B1 is principally controlled at the level of synthesis.     

Cellular and molecular mechanisms of aging: a review]

Since the beginning of this century, a large body of experimental data and observations accumulated concerning experimental and clinical gerontology. These data can be classified and analyzed according to the level of experimentation or observation as concerning aging at the molecular, cellular level or at higher levels of hierarchical organisation such as tissues, organs or the whole organism. Observations of these higher levels are mostly derived from epidemiological studies of human aging, horizontal studies or preferably vertical studies. The relative coherence of data collected at the molecular and cellular levels renders plausible a tentative of interpretation of aging phenomena at higher levels or hierarchical organisations from the tissues to the whole organism by using the data obtained at the molecular and cellular levels. The present article is a tentative for this kind or integrative interpretation of aging.     

Concentration of monoamines in the brain of minks differing in their reaction to man

Content of dopamine in the striatum; of serotonin, 5-hydroxyindolacetic acid and noradrenaline in the hypothalamus, striatum and midbrain was studied in three groups of minks from population of an animal farm, differing by their reaction to humans (cowardly, calm, aggressive). The reaction to humans was estimated by a system of marks at the attempt to catch the mink with a mitten. Aggressive animals had a lowered level of serotonin in the hypothalamus and striatum, a lesser content of serotonin metabolite--5-hydroxyindolacetic acid in the striatum. Minks of different groups did not differ by noradrenaline content, but dopamine level in the striatum of cowardly minks was higher than in calm and aggressive animals. Conclusion is made that polymorphism of behaviour corresponds to polymorphism of the state of monoaminergic systems.     

Inhibition of benzoyl peroxide/Cu2+-dependent lipid peroxidation by manganese

1. Formation of peroxides by benxoyl peroxide (BPO) and CuCl2 was examined in the human red blood cell ghost. 2. Amounts of peroxides formed increased with the amount of the ghost solution added. 3. Of all the cations tested only manganese ion inhibited the formation of peroxides in BPO-CuCl2 reaction system. 4. The formation of peroxides was inhibited approx. 50% with 0.4 microM manganese. 5. The inhibitory manner of manganese was non-competitive against copper.     

Changes in the amino acid sequence of hemagglutinin during sequential adaptation of human influenza virus A to replication in mice

The primary structure of hemagglutinin (HA) gene of Influenza virus A/USSR/90/77 (H1N1) variants after 3 and 11 passages has been determined. In the HA1 coding region of mice-adapted virus (11 passages) there are two amino acid substitutions: Thr 89----Ala and Asn 127----Asp. At the first stage of adaptation (3-rd passage) only a single mutation was detected: Asn 127----Asp. The adaptation is accompanied by the loss of specific carbohydrate attachment sites adjacent to the receptor-binding site located at HA1 subunit with a concomitant variation in antigenicity.     

Non-marine Teredolites from the Middle Eocene of southern England

Middle Eocene, non-marine sediments from southern England contain examples of Teredolites borings in two contrasting palaeoenvironmental settings, viz.: (A) as in situ borings in an allochthonous lignite in an abandoned river channel and (B) as bored logs in cross-bedded fluvial sandstones of probable point-bar origin. The lignite is 0.30 m thick, of which the upper 0.20 m is intensely bored. Rounded pebbles of ?charcoal at its base also show small borings. A log in a fluvial sandstone shows densely-packed. radial club-shaped borings. now filled with sandstone. The wood substrate has subsequently been oxidized away. To our knowledge, this is the first detailed account of Teredolites from an ancient freshwater setting.