D Baumann

Publications (3)11.62 Total impact

• Article: In vivo regulation of low-density lipoprotein receptors by estrogen differs at the post-transcriptional level in rat and mouse.

  R A Srivastava, D Baumann, G Schonfeld
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  ABSTRACT: Rats and mice are frequently used in studies of the regulation of lipoprotein metabolism. Although the species are closely related, they differ dramatically in the responses of their lipoproteins to estrogen administration. In rats, estrogens produce profound decreases in the levels of all plasma lipoproteins and this is attributed largely to estrogen-induced increases of hepatic low-density lipoprotein receptor (LDL-receptor) activity. Estrogens affect mouse plasma lipoproteins to a much lesser extent. Therefore, one of our aims was to compare the regulation of LDL-receptor gene expression in rats and mice at several potential loci of regulation. To assess the specificity of the estrogen effect, we also compared the responses of apolipoprotein AI (apoAI), apolipoprotein B (apoB), and beta-actin to the response of the LDL-receptor. In male Sprague Dawley rats given 17 beta-estradiol or 17 alpha-ethinyl estradiol at supraphysiological doses of 5 micrograms/g body mass/day, plasma total cholesterol and triacylglycerols fell to approximately 5% and approximately 50%, and, plasma apoAI and apoB fell to approximately 12% and approximately 16% of controls, respectively. By contrast, in male C3H/HeJ mice the above parameters dropped only to approximately 65% of controls and apoB concentrations rose to approximately 200% of controls. In rats, relative rates of LDL-receptor mRNA transcription (nuclear 'run-off' assay) and total hepatic, nuclear and polysomal LDL-receptor mRNA levels (RNase protection assay) increased by 1.5-2-fold, while synthesis of LDL-receptor protein on hepatic polysomes (in a wheat-germ translation system) increased 8-fold and LDL-receptor protein mass in hepatic plasma membranes increased 10-fold (by immunoblotting). In mouse liver, too, LDL-receptor mRNA levels increased 1.5-fold and the LDL-receptor mRNA transcription start sites in rat and mouse were found to be the same, but mouse LDL-receptor protein mass did not change, i.e. LDL-receptors of mice were similar to rat with respect to transcriptional regulation, but differed in their post-transcriptional control mechanisms. In rats, estrogen administration increased apoAI mRNA transcription rates 1.6-fold and also apoAI mRNA levels in total liver homogenates, nuclei and polysomes, (2-fold for each) consistent with transcriptional regulation. However, apoAI synthesis on total RNA increased less than apoAI mRNA, indicating that apoAI translational control mechanisms, at least in part, also regulate hepatic rates of apoAI production. ApoB mRNA transcription rates and levels showed small increases following estrogen administration. Hepatic beta-actin mRNA transcription and levels did not change.(ABSTRACT TRUNCATED AT 400 WORDS)
  European Journal of Biochemistry 10/1993; 216(2):527-38. · 3.58 Impact Factor
• Article: Hormonal and nutritional stimuli modulate apolipoprotein B mRNA editing in mouse liver.

  R A Srivastava, J Tang, D Baumann, G Schonfeld
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  ABSTRACT: Human livers produce apoB-100, a major protein of VLDL, while intestines produce apoB-48, the major protein of chylomicrons. ApoB-48 is translated from apoB-100 mRNAs that are post-transcriptionally edited at codon 2153, converting CAA (glutamine) to TAA, a stop codon. In contrast to humans, mouse and rat livers contain the apoB-100 mRNA editing mechanism. Because hormones and nutrients affect the metabolism of apoB containing lipoproteins, we studied the effects of sex hormones and diets on apoB mRNA editing. Groups of male and female C3H/HeJ mice were castrated and treated with 17 beta-estradiol at 0.16 (E2L) or at 5 micrograms (E2H), or with testosterone propionate at 1 microgram/g body weight/day for 14 days. Plasma apoB levels and ratios of apoB-100/apoB-48 both increased 2-fold, but only in the E2H group. To determine if the increased apoB-100/apoB-48 ratios were associated with altered levels of apoB-100 and apoB-48 mRNA, both forms of apoB mRNA were quantified. We found that indeed ApoB-100 mRNA increased 1.8-fold (p < 0.025) compared to apoB-48 mRNA only in the E2H group. Next, we studied the individual effects of dietary fatty acids and dietary cholesterol on the relative abundance of apoB-100 and apoB-48 mRNA. Contrary to the estrogen effect, the high fat-combination diet increased apoB-48 mRNA relative to apoB-100 mRNA. Total plasma apoB as well as apoB-48 synthesis in liver also increased. Our studies demonstrate that estrogens and high fat diet both modulate apoB editing in mouse liver, but that estrogens and fat diet affected apoB mRNA editing in opposite directions.
  Biochemical and Biophysical Research Communications 10/1992; 188(1):135-41. · 2.48 Impact Factor
• Source

  Available from: Jingjing Tang

  Article: In vivo regulation of apolipoprotein A-I gene expression by estradiol and testosterone occurs by different mechanisms in inbred strains of mice.

  J J Tang, R A Srivastava, E S Krul, D Baumann, B A Pfleger, R T Kitchens, G Schonfeld
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  ABSTRACT: We tested the hypothesis that testosterone and estrogen modulate apoA-I gene expression and metabolism by different mechanisms that may be influenced by genetic factors. Male and female C3H/HeJ (atherosclerosis-resistant) and C57BL/6J (atherosclerosis-susceptible) mice (n = 5/group) were castrated (Placebo). Castrates were given 17 beta-estradiol (E2) at 0.16 microgram/g (E2L) or 5 micrograms/g (E2H) body weight per day, or testosterone (Testo) 1 microgram/g per day, 14 days after surgery, for 14 days. Plasma total cholesterol concentrations (TC) were higher in male Placebo mice than in females. Testosterone altered TC and high density lipoprotein (HDL) cholesterol by gender and strain; however (HDL-C)/TC ratios and apoA-I concentrations were unaltered. Testosterone did reduce HDL particle diameters in both genders of C3H mice only. Low density lipoprotein-cholesterol (LDL-C)/TC ratios remained constant and apoB increased in males only. E2L and E2H decreased TC, HDL-C/TC ratios, and apoA-I. Decrements varied by strain. HDL diameters decreased in both genders in C3H mice only; however, HDL size distributions were altered in both strains. LDL-C/TC ratios increased in all groups. E2L mice showed variable responses of apoB, but apoB rose uniformly in all E2H groups. Testosterone increased and E2H decreased hepatic apoA-I synthesis. ApoA-I mRNA concentrations remained stable in both Testo and E2 groups. ApoA-I gene transcription varied by strain and gender, but all changes were less than twofold. Testosterone did not affect hepatic apoB or LDL receptor mRNA, however, E2H increased both mRNAs in males but not in females. On Western blotting of liver membranes, E2H had little effect on mouse LDL receptor protein mass; by contrast, E2H increased LDL receptor approximately threefold in rats. In summary, responsiveness of mouse lipids to testosterone and E2 vary by strain and gender. Testosterone and E2 differ in their regulation of apoA-I production mainly at the level of translation. Hormones operate at several levels of gene regulation, suggesting that complex mechanisms are involved. Mice differ from rats and rabbits in their LDL receptor responsiveness to estradiol treatment.
  The Journal of Lipid Research 11/1991; 32(10):1571-85. · 5.56 Impact Factor