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Bernard Bouscarel
Associate Professor
Hormones, Bile Acids, and Hepatobiliary Disorders |
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Research Interests
The Bouscarel laboratory's research program focuses on the molecular mechanism of transmembrane signal transduction by cell-surface receptors called G protein-coupled receptors (GPCRs). GPCRs allow communication between the outer and inner cell domain and trigger cellular responses. The glucagon receptor is involved in the regulation of glycogen and glucose metabolism in the liver and its response is altered in certain liver diseases, including cholestasis and cirrhosis. Using proteomic, fluorescent imaging, and biochemical, as well as pharmacological approaches, our goal is to understand what controls receptor expression, down-regulation and activity under physiologic and pathological conditions.
Furthermore, the Bouscarel laboratory¡¯s research program focuses on the mechanism of action and side effects associated to topoisomerase I inhibitors. Topoisomerase I enzymes are involved in DNA synthesis and their inhibition leads to DNA strand breaks and apoptosis. Using a variety of colonic cell lines and tumor models, our goal is to understand the mechanism regulating Topo I inhibition-induced apoptosis and the ability of certain agents to stimulate the anti-tumor effects of the Topo I inhibitor both in vitro and in vivo.
Finally, the Bouscarel laboratory¡¯s research program focuses on bile acids and their role in the modulation of hormonal response and the potency of anti-cancer drugs. The main goal is to identify novel targets useful in the development of new strategies in the treatment of liver diseases and cancer therapy.
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Selected Publications:
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Zhang Y, Ikegami T, Honda A, Miyazaki T, Bouscarel B, Rojkind M, Hyodo I, Matsuzaki Y. Involvement of integrin-linked kinase in carbon tetrachloride-induced hepatic fibrosis in rats.
Hepatology. 2006, Sep; 44(3):612-22.
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Ikegami T, Krilov L, Meng J, Patel B, Chapin-Kennedy K, Bouscarel B. Decreased glucagon responsiveness by bile acids: a role for protein kinase Calpha and glucagon receptor phosphorylation.
Endocrinology. 2006, Nov; 147(11):5294-302.
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Le M, Krilov L, Meng J, Chapin-Kennedy K, Ceryak S, Bouscarel B. Bile acids stimulate PKCalpha autophosphorylation and activation: role in the attenuation of prostaglandin E1-induced cAMP production in human dermal fibroblasts.
Am J Physiol Gastrointest Liver Physiol. 2006, Aug; 291(2):G275-87.
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Meng JP, Ceryak S, Aratsu Z, Jones L, Epstein L, Bouscarel B. Biphasic regulation by bile acids of dermal fibroblast proliferation through regulation of cAMP production and COX-2 expression level.
Am J Physiol Cell Physiol. 2006, Sep; 291(3):C546-54.
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Ikegami T, Matsuzaki Y, Al Rashid M, Ceryak S, Zhang Y, Bouscarel B. Enhancement of DNA topoisomerase I inhibitor-induced apoptosis by ursodeoxycholic acid.
Mol Cancer Ther. 2006, Jan; 5(1):68-79.
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Miyazaki T, Karube M, Matsuzaki Y, Ikegami T, Doy M, Tanaka N, Bouscarel B. Taurine inhibits oxidative damage and prevents fibrosis in carbon tetrachloride-induced hepatic fibrosis.
J Hepatol. 2005, Jul; 43(1):117-25.
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Ikegami T, Matsuzaki Y, Fukushima S, Shoda J, Olivier JL, Bouscarel B, Tanaka N. Suppressive effect of ursodeoxycholic acid on type IIA phospholipase A2 expression in HepG2 cells.
Hepatology. 2005, Apr; 41(4):896-905.
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Miyazaki T, Matsuzaki Y, Ikegami T, Miyakawa S, Doy M, Tanaka N, Bouscarel B. Optimal and effective oral dose of taurine to prolong exercise performance in rat.
Amino Acids. 2004, Dec; 27(3-4):291-8.
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Miyazaki T, Matsuzaki Y, Ikegami T, Miyakawa S, Doy M, Tanaka N, Bouscarel B. The harmful effect of exercise on reducing taurine concentration in the tissues of rats treated with CCl4 administration.
J Gastroenterol. 2004, Jun; 39(6):557-62.
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Miyazaki T, Matsuzaki Y, Karube M, Bouscarel B, Miyakawa S, Tanaka N. Amino acid ratios in plasma and tissues in a rat model of liver cirrhosis before and after exercise.
Hepatol Res. 2003, Nov; 27(3):230-237.
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Matsuzaki Y, Miyazaki T, Ohkoshi N, Miyakawa S, Bouscarel B, Tanaka N. Degeneration of skeletal muscle fibers in the rat administrated carbon tetrachloride: similar histological findings of the muscle in a 64-year-old patient of LC with muscle cramp.
Hepatol Res. 2002, Dec; 24(4):368-378.
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Matsuzaki Y, Bouscarel B, Ikegami T, Honda A, Doy M, Ceryak S, Fukushima S, Yoshida S, Shoda J, Tanaka N. Selective inhibition of CYP27A1 and of chenodeoxycholic acid synthesis in cholestatic hamster liver.
Biochim Biophys Acta. 2002, Nov 20; 1588(2):139-48.
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Matsuzaki Y, Miyazaki T, Miyakawa S, Bouscarel B, Ikegami T, Tanaka N. Decreased taurine concentration in skeletal muscles after exercise for various durations.
Med Sci Sports Exerc. 2002, May; 34(5):793-7.
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Ikegami T, Ha L, Arimori K, Latham P, Kobayashi K, Ceryak S, Matsuzaki Y, Bouscarel B. Intestinal alkalization as a possible preventive mechanism in irinotecan (CPT-11)-induced diarrhea.
Cancer Res. 2002, Jan 1; 62(1):179-87.
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Ikegami T, Cypess AM, Bouscarel B. Modulation of glucagon receptor expression and response in transfected human embryonic kidney cells.
Am J Physiol Cell Physiol. 2001, Oct; 281(4):C1396-402.
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Kobayashi K, Ceryak S, Matsuzaki Y, Kudoh S, Bouscarel B. Effect of bile acids on the uptake of irinotecan and its active metabolite, SN-38, by intestinal cells.
Biochim Biophys Acta. 2001, Feb 16; 1525(1-2):125-9.
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Ceryak S, Bouscarel B, Malavolti M, Robins SJ, Caslow KL, Fromm H. Effect of ursodeoxycholic acid on hepatic LDL binding and uptake in dietary hypercholesterolemic hamsters.
Atherosclerosis. 2000, Nov; 153(1):59-67.
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