Beta-glucuronidase activity and its variation with pH in human atherosclerotic arteries

Miller, Benjamin F.; Aiba, Tsuneo; Keyes, F.P.; Curreri, P. William; Branwood, A. W.

doi:10.1016/s0368-1319(66)80046-7

Cited by 19 publications

(2 citation statements)

References 14 publications

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confidence: 99%

Increased Activity of Lysosomal Enzymes in Experimental Atherosclerosis, and the Effect of Cortisone

Pw¹,

Hv²,

Mj³

et al. 1969

Experimental Biology and Medicine

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The activity of beta-glucuronidase is increased in atherosclerotic human arteries (1)(2)(3) . Noting that beta-glucuronidase is a key marker enzyme in evaluating lysosomal enzyme activity, we decided to investigate other lysosomal enzymes in human atherosclerotic vessels. I t was found that in addition to beta-glucuronidase, the lysosomal enzymes, acid phosphatase, cathepsin and aryl sulfatase showed increased activity in human atherosclerotic aortas (4). The present report describes the activities of these four enzymes in the aortas of rabbits in which atherosclerosis has been induced by adding cholesterol to the diet.The effect of cortisone added to the diet has been observed. Cortisone tends to increase the level of serum cholesterol in the cholesterol-fed animals; nevertheless, this compound greatly decreases the intensity of atherosclerosis (5, 6 ) . I t is of interest that cortisone exerts a strong effect on lysosomal membranes (7). We have therefore investigated the effect of cortisone on the activity of the lysosomal enzymes in the cholesterol-fed rabbits.Materials and Methods. Male, white New Zealand rabbits, weighing 2.0 to 2.5 kg were fed the diets ad libitum for a period of 100 days. The control group of 5 rabbits received standard rabbit chow. Another 10 animals were fed the same chow to which was added 1 c/r cholesterol acetate. Of these, five survived the 100-day. period. A third group of 8 rabbits received the cholesterol-containing diet to which was added cortisone acetate to give a concentration of 0.005%]. Of the third group, 5 rabbits were alive a t the end of the experiment. The animals were sacrificed instantly by mechanical means a t 100 days. *Aided by a grant from The William H. Donner Foundation.The aortas were dissected out and scored grossly with a hand lens for atherosclerotic involvenient by two observers working independently. The arch, the thoracic and abdominal portions of the aorta were graded separately on a scale of 1 to 4, and the total score was recorded: 1+ represents fatty streaks and small plaques covering up to 10% of the area; 2+ indicates 10-25%; 3+, 25-50%; 4+ from 50% to total involvement.Representative samples of each portion of the aorta were taken for histologic examination, and the remainder were employed for the enzyme assays. The histological examinations were performed by Dr. M. A. Farooki, Professor of Pathology, Khyber Medical College, Peshawar University, who a t the time of these experiments was Visiting Pathologist at the Philadelphia General Hospital.For the determination of enzyme activities, the aortas were carefully stripped of adventitia. The intima-media residuals were then homogenized by hand in a cold 0.25 M sucrose solution with a glass tissue grinder. The homogenate was centrifuged a t 2520g for 10 min to remove debris. The supernatant was employed for the estimation of the enzyme activities. The enzymic tests were all carried out a t 37". Activities are expressed in units//gram of tissue; 1 unit refers to the decomposition of 1 pg or 1 pmole of ...

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confidence: 99%

Increased Activity of Lysosomal Enzymes in Experimental Atherosclerosis, and the Effect of Cortisone

Pw¹,

Hv²,

Mj³

et al. 1969

Experimental Biology and Medicine

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“…Contemporaneous scientific publications, however, provide the context: elevated urinary beta-glucuronidase had been found to be positively associated with bladder cancer [ 36 , 37 ]. There was also some evidence that beta-glucuronidase activity was associated with atherosclerosis [ 38 ]. This incidental finding of Project 259 demonstrated to SRF that sucrose versus starch consumption caused different metabolic effects and suggested that sucrose, by stimulating urinary beta-glucuronidase, may have a role in the pathogenesis of bladder cancer.…”

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Sugar industry sponsorship of germ-free rodent studies linking sucrose to hyperlipidemia and cancer: An historical analysis of internal documents

2017

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In 1965, the Sugar Research Foundation (SRF) secretly funded a review in the New England Journal of Medicine that discounted evidence linking sucrose consumption to blood lipid levels and hence coronary heart disease (CHD). SRF subsequently funded animal research to evaluate sucrose’s CHD risks. The objective of this study was to examine the planning, funding, and internal evaluation of an SRF-funded research project titled “Project 259: Dietary Carbohydrate and Blood Lipids in Germ-Free Rats,” led by Dr. W.F.R. Pover at the University of Birmingham, Birmingham, United Kingdom, between 1967 and 1971. A narrative case study method was used to assess SRF Project 259 from 1967 to 1971 based on sugar industry internal documents. Project 259 found a statistically significant decrease in serum triglycerides in germ-free rats fed a high sugar diet compared to conventional rats fed a basic PRM diet (a pelleted diet containing cereal meals, soybean meals, whitefish meal, and dried yeast, fortified with a balanced vitamin supplement and trace element mixture). The results suggested to SRF that gut microbiota have a causal role in carbohydrate-induced hypertriglyceridemia. A study comparing conventional rats fed a high-sugar diet to those fed a high-starch diet suggested that sucrose consumption might be associated with elevated levels of beta-glucuronidase, an enzyme previously associated with bladder cancer in humans. SRF terminated Project 259 without publishing the results. The sugar industry did not disclose evidence of harm from animal studies that would have (1) strengthened the case that the CHD risk of sucrose is greater than starch and (2) caused sucrose to be scrutinized as a potential carcinogen. The influence of the gut microbiota in the differential effects of sucrose and starch on blood lipids, as well as the influence of carbohydrate quality on beta-glucuronidase and cancer activity, deserve further scrutiny.

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Subcellular Fractionation Studies on the Cells Isolated from Normal and Atherosclerotic Aorta

Takano

Duve

1973

Novartis Foundation Symposia

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Beta-glucuronidase activity and its variation with pH in human atherosclerotic arteries

Cited by 19 publications

References 14 publications

Increased Activity of Lysosomal Enzymes in Experimental Atherosclerosis, and the Effect of Cortisone

Increased Activity of Lysosomal Enzymes in Experimental Atherosclerosis, and the Effect of Cortisone

Sugar industry sponsorship of germ-free rodent studies linking sucrose to hyperlipidemia and cancer: An historical analysis of internal documents

Subcellular Fractionation Studies on the Cells Isolated from Normal and Atherosclerotic Aorta

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