Modifying Influence of Fasting on DNA Synthesis, Cholesterol Metabolism and HMP Shunt Enzymes in Liver Hyperplasia Induced by Lead Nitrate

Dessı̀, Sandra; Batetta, Barbara; Pulisci, D.; Carrucciu, A.; Armeni, Marina; Mulas, Michela; Pani, P.

doi:10.1007/978-1-4757-9640-7_57

Cited by 2 publications

(3 citation statements)

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“…In all animal models, cholesterol synthesis and esterification as well as HDL-C were taken into account. We found an increase of cholesterol synthesis and esterification during liver regeneration following partial hepatectomy [66], in liver hyperplasia occurring after a single administration of lead nitrate [67,68], and in the liver of diabetic rats given insulin as well as in that of fasting rats [69,70]. In all these models, the peak of synthesis clearly preceded the maximum incorporation of labelled thymidine into DNA and accompanied all proliferative processes.…”

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confidence: 84%

Cholesterol metabolism during cell growth: Which role for the plasma membrane?

Batetta

Sanna

2006

Euro J Lipid Sci & Tech

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Parenchyma proliferation is accompanied by a peculiar modification of the cholesterol metabolism involving both the growing tissue and the plasma compartment. The increase of cholesterol synthesis and uptake has been largely described in the literature and mainly ascribed to the increased requirement of cholesterol for new membrane biogenesis. The dramatic reduction of cholesterol efflux, which probably contributes to the increase of cholesterol esterification and accumulation, has also been largely described, although, further to acting as a prompt pool for membrane biogenesis requirements, its significance and possible influence on cholesterol homeostasis during growth has been almost completely neglected. In this short review, the most widely known modifications and new insights into the cholesterol metabolism during the growth of normal and tumoral cells will be discussed. Particular attention will be paid to the most widely known modifications of cholesterol storage and efflux. The possible implication of proteins in membrane cholesterol translocation causing cholesterol to be directed towards the ER for esterification by ACAT rather than being released by the appropriate external acceptor, i.e. HDL, during proliferation will be discussed. Keywords:Membrane cholesterol, HDL-C, cell proliferation, signal transduction. Cholesterol metabolism in non-growing cellsWith the exception of specialised cells such as hepatocytes, the majority of resting cells synthesise cholesterol only virtually, with the minimal amounts of the required sterols being obtained by an external source (via lowdensity lipoprotein (LDL) receptor), intracellular cholesterol esterification and efflux also being absent, in accordance with the low membrane turnover present in this condition. Under normal conditions, intracellular cholesterol homeostasis utilises a complex network of reactions capable of providing an adequate supply of cholesterol while avoiding possible conditions of toxicity for the cells. In the majority of cells, the cholesterol supply is regulated by the balance between endogenous synthesis in the endoplasmic reticulum (ER), under the control of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCoA-R), and uptake of exogenous cholesterol, involving endocytosis of the LDL receptor (LDL-r) complex [1]. Toxic conditions produced by excess free cholesterol can be avoided in several ways: by down-regulating cholesterol synthesis and uptake, by promoting esterification by acyl-CoA:cholesterol acyltransferase (ACAT) in the ER [2], and/or by transport to the plasma membrane with subsequent delivery to an external acceptor, i.e. highdensity lipoproteins (HDL) [3].However, it is a well-established fact that a pool of cholesterol completes a cycle to the membrane and returns to the ER with a half-time of 40 min [4], and numerous studies have been undertaken to clarify the mechanisms and the proteins involved in the transport of such a highly hydrophobic lipid between the various intracellular compartments [5][6][7].With regard to cholester...

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confidence: 84%

Cholesterol metabolism during cell growth: Which role for the plasma membrane?

Batetta

Sanna

2006

Euro J Lipid Sci & Tech

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“…Mutations in the gene result in an increased susceptibility to oxidative stress due to the loss of NADPH and its ability to reduce free radicals and peroxides. In humans, the disease associated with a partial loss of G6PD activity is known as Favism (123,124). The disease is caused by point mutations in the G6PD gene, and diminishes (but does not abolish) the activity of the enzyme.…”

Section: G6pd: Regulation By a Posttranscriptional Mechanismmentioning

confidence: 99%

“…The disease is caused by point mutations in the G6PD gene, and diminishes (but does not abolish) the activity of the enzyme. G6PD-deficiency results in reduced serum lipoprotein levels, demonstrating the importance of G6PD in generating NADPH for fatty acid synthesis (123). Chronic non-spherocytic hemolytic anemia can also occur in individuals with more severe mutations, again emphasizing the important role of NADPH in defending against oxidative stress (125).…”

Section: G6pd: Regulation By a Posttranscriptional Mechanismmentioning

confidence: 99%

Mechanism by which dietary polyunsaturated fat regulates lipogenic gene expression

Kohan¹

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Primary hepatocytes treated with non-esterified polyunsaturated fatty acids have been used as a model for describing the inhibitory effects of dietary polyunsaturated fats on lipogenic gene expression. This model resembles starvation or uncontrolled diabetes but not dietary fat ingestion, which is delivered to liver via chylomicron remnants. Chylomicron remnants enriched with polyunsaturated fatty acids stimulate a unique pattern of intracellular signaling. These remnants enhance p38 mitogen activated protein kinase (MAPK) activity but do not inhibit insulin signaling or induce extracellular-signal related kinase (ERK) or AMP-activated protein kinase (AMPK) activation as do non-esterified polyunsaturated fatty acids. Polyunsaturated fatty acids-enriched remnants and non-esterified polyunsaturated fatty acids both inhibit the rate of fatty acid synthesis and the expression of the lipogenic genes, particularly those regulated by sterol response element binding protein-1c (SREBP-1c). Saturated fatty acid-enriched remnants fail to inhibit the lipogenic genes indicating that the inhibitory action of dietary polyunsaturated fats involves regulatory mechanisms in liver. In contrast, polyunsaturated fatty acids-enriched remnants fail to inhibit malic enzyme, glucokinase, L-pyruvate kinase, and cytochrome P450-7α (Cyp-7α) expression despite their inhibition by non-esterified fatty acids. These genes are regulated independently of SREBP-1c. Therefore, non-esterified polyunsaturated fatty acids do not accurately model all aspects of regulation of hepatic metabolism by dietary fat. Alison Bloom Kohan Mechanism by which Dietary Polyunsaturated Fat Regulates Lipogenic Gene Expression iii ACKNOWLEDGEMENTS I would like to thank all those people who have supported me throughout my Ph.D training. First, I am very thankful for all the help and advice that I have received from my advisor Dr. Lisa Salati in these last 6 years. I have learned how best to teach, learn, and participate in scientific endeavors through her. I appreciate all the time and effort she took to train me from an inexperienced graduate student to the doctoral graduate I am today. I also want to thank all of my lab mates who have made my work in the lab so much more fulfilling. Callee, Viola, and Sushant have at times been my biggest fan club, my most helpful reviewers, and my best critics. At all times, they have been my friends. Without them, I'm not sure how I could have made it through to my defense. I'll miss our scientific discussions, but also they're daily friendship as I start in a new lab. Finally, I want to thank my family. Without the continuous support of my parents, my inlaws, and my husband I could not have succeeded at this goal. My husband Mark, especially, has been an incredible source of strength, support, and love throughout this process. He has always reminded me why I chose this path, and he has always helped me to stay on it. Without him, this would not be possible. ABSTRACT iii. TABLE OF CONTENTS iv. ABBREVIATIONS vi. CHAPTER 1. 1 I. SIGNIF...

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Modifying Influence of Fasting on DNA Synthesis, Cholesterol Metabolism and HMP Shunt Enzymes in Liver Hyperplasia Induced by Lead Nitrate

Cited by 2 publications

References 12 publications

Cholesterol metabolism during cell growth: Which role for the plasma membrane?

Cholesterol metabolism during cell growth: Which role for the plasma membrane?

Mechanism by which dietary polyunsaturated fat regulates lipogenic gene expression

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