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Biomedical subjects

M Golan

Publications and source records attributed to M Golan.

34 records · Page 2Linked to original sources
PubMed1985

Metabolism of benzo(a)pyrene by subcellular fractions of rat liver: evidence for similar patterns of cytochrome P-450 in rough and smooth endoplasmic reticulum but not in nuclei and plasma membrane.

Since our earlier work (P. Stasiecki, F. Oesch, G. Bruder, E.D. Jarasch, and W.W. Franke, Eur. J. Cell Biol., 21: 79-92, 1980) had shown that carcinogen-metabolizing monooxygenase activity was present in almost all investigated cellular membranes, the possibility of differential control of the various metabolic pathways in the individual cellular membranes arose. Using high pressure liquid chromatography we have now studied the benzo(a)pyrene metabolites formed by rough and smooth endoplasmic reticulum, nuclei, and plasma membrane as well as mitochondrial fractions and investigated the metabolic cooperation between the monooxygenases and epoxide hydrolase in these fractions. Since various cytochrome P-450 isozymes catalyze the oxidative attack on the benzo(a)pyrene molecule at defined preferential sites, this analysis also provides an indirect trace of potential differences in the pattern of cytochrome P-450 isozymes present in the individual membranes. The metabolic profiles produced by the two most active fractions, smooth and rough endoplasmic reticulum, were very similar to each other but different from those produced by the other three preparations. The metabolite pattern produced by incubations containing nuclear fractions differed slightly from that produced by the fractions of endoplasmic reticulum, but plasma membrane and mitochondria produced markedly different patterns. Since the similarity of the benzo(a)pyrene metabolite pattern produced by the smooth and rough endoplasmic reticulum suggested similar cytochrome P-450 isozyme patterns in these two subfractions, they were further investigated by the use of selective inducers as well as a broad spectrum substrate, 7-ethoxy-coumarin, in the absence and presence of selective inhibitors. Treatment of animals with trans-stilbene oxide or phenobarbital (a) increased the total amount of metabolites per protein mass and time, (b) changed the pattern of metabolites, but (c) induced a pattern of metabolites which was again very similar in rough and smooth endoplasmic reticulum. Even more distinct changes were found following treatment with 3-methylcholanthrene or beta-naphthoflavone. Both of these compounds (a) preferentially induced the activity of rough endoplasmic reticulum, (b) changed the profile of metabolites, but (c) again did not disturb the similarities of the benzo(a)pyrene metabolite pattern between both fractions.(ABSTRACT TRUNCATED AT 400 WORDS)

7-Alkoxycoumarin O-Dealkylase↗
PubMed1982

The mutagenicity of dibenz [a,h]anthracene activated by phenobarbital-inducible mouse-liver mono-oxygenase is potentiated by the presence of hydrophilic residues at the K-region of the molecule.

Dibenz[a,h]anthracene and synthetic K-region derivatives of the parent hydrocarbon and of benz[a]anthracene were tested for mutagenicity by the reversion of histidine-dependent Salmonella typhimurium TA98, TA100 and TA1537. The K-region metabolite 5,6-dihydroxy-5,6-dihydrodibenz[a,h]anthracene, inactive as such, was efficiently activated to mutagens for TA98 and TA100 by mouse-liver 9000 X g supernatant or microsomal fraction. Microsomes from phenobarbital- or Aroclor-1254-treated mice were efficient for this activation, while those from untreated or beta-naphthoflavone-treated mice were much less active. A study on the influence of various structural features on this efficient activation by phenobarbital-inducible mono-oxygenase of mouse-liver microsomes showed that, if the K-region were saturated, no metabolism to mutagens occurred, while substitution of the K-region by carbonyl and hydroxyl substituents led to increased mutagenic efficacy with increasing hydrophilicity (dihydro less than carbonyl less than hydroxyl). The K-region epoxide was the only derivative that did not require metabolic activation and it had a markedly different mutagenic specificity in that it was also mutagenic for TA1537.

Animals↗
PubMed1980

Specificity of mouse liver cytosolic epoxide hydrolase for K-region epoxides derived from polycyclic aromatic hydrocarbons.

Mouse liver cytosol epoxide hydrolase, known to be very active for certain alkene oxides, had a specific activity which was 2.1-, 11- and 160-fold lower than that of the microsomal epoxide hydrolase for the arene oxides 7-methylbenz[a]anthracene 5,6-oxide, benz[a]anthracene 5,6-oxide and phenanthrene 9,10-oxide, respectively. For benzo[a]pyrene 4,5-oxide no activity (less than 10 pmol product/mg protein/min) of cytoplasmic epoxide hydrolase was detectable. The specific activity of cytoplasmic epoxide hydrolase was much lower for all K-region epoxides investigated, compared to trans-stilbene oxide used as a positive control and for which a new assay is described. It is concluded from these rates combined with the fact that these lipophilic K-region epoxides are expected to stay preferentially at membranous sites where they are generated, that cytoplasmic epoxide hydrolase plays a minor role for their transformation compared to membrane-bound hydrolase. The data also show that for the substrates investigated the epoxide hydrolase activities in the cytoplasmic and microsomal fractions are complementary to some extent, but there is no quantitative inverse relationship.

Animals↗
PubMedDate not supplied

Familial approach to the treatment of childhood obesity: conceptual mode.

This model for the management of childhood obesity uses a family-based approach. Change is delivered through the parents (instead of the obese child) emphasizing a healthy lifestyle and not weight reduction as in previously published, family-based management of childhood obesity. This intervention integrates behavioral, social learning, and family system approaches. The proposed approach includes changes in parental cognition, emphasizing "parenthood presence"; parents serve both as a source of authority and a role model for the obese child, providing a family environment that fosters healthy practices related to weight control issues and de-emphasizing personal responsibility for control of health behavior.

Child↗