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R J Cenedella

Publications and source records attributed to R J Cenedella.

95 records · Page 6Linked to original sources
PubMedDate not supplied

Cholesterol and cataracts.

Inherited defects in enzymes of cholesterol metabolism and use of drugs which inhibit lens cholesterol biosynthesis can be associated with cataracts in animals and man. The basis of this relationship apparently lies in the need of the lens to satisfy its sustained requirement for cholesterol by on-site synthesis, and impairing this synthesis can lead to alteration of lens membrane structure. Lens membrane contains the highest cholesterol content of any known membrane. The Smith-Lemli-Opitz syndrome, mevalonic aciduria, and cerebrotendinous xanthomatosis all involve mutations in enzymes of cholesterol metabolism, and affected patients can develop cataracts. Two established models of rodent cataracts are based on treatment with inhibitors of cholesterol biosynthesis. The long-term ocular safety of the very widely used vastatin class of hypocholesterolemic drugs is controversial. Some vastatins are potent inhibitors of cholesterol biosynthesis by animal lenses, can block cholesterol accumulation by these lenses and can produce cataracts in dogs. Whether these drugs inhibit cholesterol biosynthesis in human lenses at therapeutic doses is unknown. Results of clinical trials of 1-5 years duration in older patient populations indicate high ocular safety. However, considering the slow life-long growth of the lens and its continuing need for cholesterol, longterm safety of the vastatins should perhaps be viewed in units of 10 or 20 years, particularly with younger patients.

Animals↗
PubMedDate not supplied

Specific labeling of lens aldehyde dehydrogenase class 1 from (3)H-cholesterol or its derivatives.

We investigated the possibility that sterols could covalently modify ocular lens cell proteins. Incubation of cultured bovine lens epithelial cells (BLEC) with (3)H-cholesterol led to the labeling of a cytosolic protein of about 52 kD. Two-dimensional electrophoresis of the BLEC soluble proteins and fluorography revealed one labeled protein of 52 kD, pI = 6.6, plus a weakly labeled, slightly more acidic protein of the same size. MALDI-MS analysis of both proteins recovered from duplicate gels indicated both to be aldehyde dehydrogenase class 1 (ALDH-1). The identity was confirmed by immunoprecipitation with antiserum to ALDH-1. Alkaline hydrolysis of (3)H-labeled ALDH-1 released most of the radiolabel as compounds much more polar than cholesterol. We speculate that lens ALDH-1 can participate in the oxidation of cholesterol or its derivatives to unidentified sterol carboxylic acids and that the labeled protein reflects capture of ALDH-1 with sterol intermediates covalently bound to the enzyme in ester linkage. Lens ALDH-1 might, therefore, participate in the detoxication of polar sterols.

Aldehyde Dehydrogenase↗