Липофусцин в старении и патологии

• Автор: Татарюнас, Антанас Бернардович
• Шифр специальности: 03.00.02
• Научная степень: Докторская
• Год защиты: 1998
• Место защиты: Вильнюс
• Количество страниц: 210 с. : ил.; 21х15 см

ANTANAS TATARIUNAS
lipofuscin in aging and pathology
Vilnius 1998
Ta 227 Tatariunas, Antanas
UDK 577 2/ 3 Lipofuscin in aging and pathology. Vilnius: The Publishing House of the Seimas, 1998.-210 p.
In this book we have a description of Ceroid-Lipofuscin cytosomes which were examined by the prism of discovered photophenomenon of increased intrinsic fluorescense. The book is illustrated with 84 figures, 11 tables and one scheme. Includes 417 bibliographical references.
ISBN
P0Cm$QK№
© A. Tatariunas, 1998. © The Publishing House of the Seimas, 1998.
All rights reserved. No part of this book may be reproduced in any form or by any means without permissions in writing from the author or publishers.
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INTRODUCTION
lipid polymer”. It was also proposed that this polymer was the “stored substance” in the CLN. In retrospect, the designated “acidic lipid polymer” turned to be the cMT-ATPe proteolipid.
For many years the CLG in the CLN had been referred to as Ceroid because of similar staining and fluorescent properties originally described in cirrhotic livers and vitamin E deficiency [217]. With this background, there was an associated postulate that pigmentogenesis was primarily associated with the oxidation of lipids. The pathogenesis of CLG in animal CLN is now distanced from the pathogenesis of Ceroid as originally conceived [228, 229]. Thus, Prof. Jolly’s Laboratory in New Zealand used the descriptive term “proteolipid proteinosis” [226] instead of the term “ceroid-lipofuscinosis”. Nevertheless, a group of “subunit c storage diseases” is now clearly established [228, 229].
Recently it has been shown [233] that CLG storage material from cerebral cortex of human beings with the late infantile form of CLN disease is also mainly a protein. It consists of a mixture of polypeptides ranging in apparent molecular weight from 13 to 67 kDa. Most of the prominent bands observed had apparent molecular weights between 37 and 52 kDa. The major unique feature of the storage polypeptides was the presence of covalently-bound S-methylmethionine [(3-amino-3-carboxypropyl)dimethyl sulfonium ion], a sulfonium compound. This compound is also called vitamin U. It is known that a post-translational methy-lation of proteins at the amino groups of constituent amino acids is a frequent occurence [234], but S-methylation of methionine residues typically does not occur in animal tissues [235]. Thus, CLG protein methionine S-methylation appears to be a unique feature of this disease. It is well known that covalent modification of proteins can block their proteolytic degradation and also affect the transportation of specific proteins into mitochondria [234, 235]. Inappropriate S-methylation of CLG storage proteins impairs their transportation into mitochondria and thus accounts for its accumulation in storage cytosomes. How these storage S-methylated proteins are transported by CLG or other membranes is still unknown.
In 1970-80, accumulation of retinoids/carotenoids in CLG during aging was established [38-50]. Recently, the other isoprenoids such as Dol-OH and Dol-P in CLG have been the object of several studies. Dolichols [51], typical isoprenoids from the nonsaponifiable fraction of lipids, are characterized as a family of Cg0-C100 polyisoprenols containing an a-saturated isoprene residue (Fig. 1-3). Dolichols are not vitamins and can be synthesized endogenously in cell microsomes.