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1.1 Tuesday 24th June 1997



Regulation of RNA polymerases I and III by the retinoblastoma protein: a mechanism for growth control?

White RJ

Institute of Biomedical and Life Sciences, University of Glasgow, UK.

Trends Biochem Sci 22 (3): 77-80 (Mar 1997)

The retinoblastoma protein, RB, is an important tumour suppressor. Recent studies have shown that it inhibits the synthesis of both rRNA and tRNA by RNA polymerases I and III. Suppression of these important determinants of biosynthetic capacity might provide a mechanism for restraining cell growth. Loss of this control could constitute one step towards tumour progression.

PMID: 9066256, MUID: 97218894


Changes with age in the structure of fibromodulin in human articular cartilage.

Roughley PJ, White RJ, Cs-Szabo G, Mort JS

Genetics Unit, Shriners Hospital for Crippled Children, Montreal, Quebec, Canada.

Osteoarthritis Cartilage 4 (3): 153-161 (Sep 1996)

An anti-peptide antibody was raised in a rabbit against the carboxy terminal region of the human fibromodulin core protein. The antibody was purified from other components of the resulting antiserum by affinity chromatography using the immobilized peptide, and was used to study the structural heterogeneity of fibromodulin extracted from human articular cartilage of different ages by the use of immunoblotting following sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis of the extracted macromolecules. In the fetus and neonate, fibromodulin was visualized as a diffuse component with a relative molecular weight of 70-110 kDa, whereas in the mature adult a more discrete component of smaller size was apparent with a relative molecular weight of 67 kDa. The size of the fibromodulin from mature adult cartilage could not be altered by pretreatment of the samples with keratanase II or endo-beta-galactosidase before analysis. In contrast, the size of the fibromodulin from younger cartilage could be decreased with both glycosidases, with the endo-beta-galactosidase yielding a smaller product than the keratanase. The size of the product resulting from endo-beta-galactosidase treatment of the fibromodulin from young adult cartilage. Thus, fibromodulin is present in human articular cartilage at all ages, but the extracted molecules only appear to exist in a proteoglycan form possessing keratan sulfate chains in the juvenile and young adult, and the size of these chains decreases with age. In the mature adult the fibromodulin does not possess either keratan sulfate or non-sulfated polylactosamine chains, though it appears to possess the same number of N-linked oligosaccharides as its counterparts from the younger tissue, but they are not modified further. The majority of the fibromodulin extracted from arthritic cartilage is of the same size as that found in the normal mature adult, although there is evidence for proteolytic processing. The degree of such processing is greater for the fibromodulin obtained from the cartilage of rheumatoid arthritic joints than osteoarthritic joints.

PMID: 8895216, MUID: 97050488


Aging-related decrease in liver peroxisomal fatty acid oxidation in control and clofibrate-treated mice. A biochemical study and mechanistic approach.

Perichon R, Bourre JM

INSERM U26, Hopital Fernand Widal, Paris, France.

Mech Ageing Dev 87 (2): 115-126 (Jun 7 1996)

Membrane fatty acid composition affects membrane structure and function. Alterations in membrane composition have been reported in old animals and it is now hypothesized that these alterations may contribute to the onset of age-related diseases. Previously, we proposed that peroxisomes might also be involved in these aging-related membrane alterations. In order to extend our previous work, we have assayed acyl-CoA oxidase activity and cyanide-insensitive fatty acid oxidation activity for both arachidonic 20:4(n-6) and docosahexaenoic 22:6(n-3) acids, catalase and urate laurate hydroxylase activity in the liver of young and old mice fed either a control or a clofibrate-supplemented diet. Our results suggest a progressive general decrease in peroxisomal function during aging, including a decrease in the fatty acid oxidation pathway that takes place via a specific decrease in acyl-CoA oxidase activity. The aging-related decrease in peroxisomal function is linked to a concomitant decrease in cytochrome P4504A laurate hydroxylase activity in control animals but not in clofibratetreated mice. This suggests aging impairs a mechanism in peroxisome proliferation that is subsequent to the cytochrome P4504A step. Implications of the aging-related peroxisomal fatty acid oxidation decrease on health through possible alterations in membrane composition and function and very long chain fatty acid accumulation are discussed.

PMID: 8783194, MUID: 96377347


Peroxisomal beta-oxidation activity and catalase activity during development and aging in mouse liver.

Perichon R, Bourre JM

Laboratoire de Neurotoxiologie, INSERM U26, Hopital Fernand Widal, Paris,France.

Biochimie 77 (4): 288-293 (1995)

Liver peroxisomal beta-oxidation activity on stearate, oleate, linoleate and alpha-linolenate was investigated as a function of age in two mouse strains. Each fatty acid showed a similar beta-oxidation activity pattern with age characterized by a rapid increase (200%) from day 2 to 20 followed by a dramatic weaning-related decrease (70%) from day 20 to 22. There was a new increase (260%) from day 22 to 75, then a plateau up to day 300 days, and finally an age-related decrease (70%) from day 300 to 540. Oleic, linoleic and alpha-linolenic acids were respectively 5-, 7.5- and 9-fold more degraded than stearic acid. Catalase specific activity showed the same age-related pattern as fatty acid beta-oxidation. Both mouse strains showed the age-related decreases. The longer-lived strain exhibited higher activity for both peroxisomal beta-oxidation and catalase and the rate of decrease of these two activities during aging was the same for both strains. The catalase/alpha-linolenic acid beta-oxidation ratio was constant during adulthood and aging. These results suggest that peroxisomal beta-oxidation and catalase activities are closely related throughout and implications for long-chain and very long-chain fatty acid metabolism, maintenance of membrane fatty acid composition and anti-oxidant status during aging are discussed.

PMID: 8589059, MUID: 96172681


Alterations in eighteen-carbon saturated, monounsaturated and polyunsaturated fatty acid peroxisomal oxidation in mouse brain during development and aging.

Bourre JM, Piciotti M

INSERM U 26, Hopital Fernand Widal, Paris.

Biochem Mol Biol Int 41 (3): 461-468 (Mar 1997)

Peroxisomal oxidation was measured in mouse brain homogenate by adding cyanide to the test tube (which inhibits mitochondrial oxidation). Eighteen-carbon fatty acids (saturated, monounsaturated and polyunsaturated) were oxidized by brain peroxisomes. At nearly all ages, oxidation of oleic acid was higher (about 2 fold) than oxidation of other eighteen-carbon fatty acids. In contrast to other fatty acids, stearic acid oxidation decreased regularly up to weaning (6 fold) and was stable thereafter. Oleic acid oxidation increased up to weaning, decreased during development up to day 70 and remained subsequently nearly stable. Linoleic acid and alpha-linolenic acid oxidation increased up to weaning,decreased up to day 105 and was nearly stable thereafter. Alpha-linolenic acid oxidation about was two fold lower than linoleic acid oxidation. Interestingly, peroxisomal oxidation for all fatty acids examined declined during aging, between day 365 and day 450.

PMID: 9090453, MUID: 97245798



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