Journal of Nutrition and Health

The Korean Nutrition Society (한국영양학회)
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Functional Studies of Acyl-CoA Synthetase 4 in the Rat Liver

흰쥐 간장에 있어서 아실-CoA 합성효소4의 기능연구

  • 정영희 (전남대학교 농업생명과학대학 동물자원학부) ;
  • 문승주 (생물공학연구소) ;
  • 강만종 (농업과학기술연구소)
  • Published : 2003.05.01
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Abstract

Acyl-CoA synthetase 4 (ACS4) is an arachidonate-preferring enzyme abundant in steroidogenic tissues. We examined ACS4 in rat liver, which contains a variety of pathways that use acyl-CoAs, in order to determine subcellular locations. We demonstrate that ACS4 protein was present most abundantly in the mitochondria and to a much lesser extent in the peroxisomes and microsomes. To determined the dietary effects on the level of ACS4 mRNA, northern blotting was carried out using total RNA from the livers of adult male rats fed various diets. Fasting, high fat diet, and fat-free high sucrose diet increased the hepatic level of ACS4 mRNA approximately 2-fold. Furthermore, the levels of ACS4 mRNA were induced by DEHP[Di- (2-ethylhexyl) phthalate]. These data suggest that ACS4 expression in the liver is regulated with a variety of pathways, including $\beta$-oxidation, hormone, and insulin.

본 연구에서는 흰쥐 간장에 있어서 아실-CoA 합성효소 4의 세포내 소기관의 존재 여부를 확인함과 동시에 fasting, high fat diet, fat-free high sucrose diet, 퍼옥시솜 증식 인자인 DEHP [Di-(2-ethylhexyl)phthalate]를 급여한 흰쥐 간장에 있어서 ACS4의 발현에 대하여 조사하였다. ACS4는 ACSI과 마찬가지로 흰쥐 간장의 마이크로솜, 미토콘드리아와 퍼옥시솜에 존재하는 것으로 생각되며 미토콘드리아에서 가장 많은 단백질이 검출되었다. ACS4 mRNA는 절식하였을 때와 high fat diet, fat-free high sucrose diet을 급여하였을 때는 대조군에 비하여 2.3배 발현이 증가하였으며 DEHP을 급여하였을 때는 3.9배 mRNA의 증가를 나타내었다. 이러한 결과를 종합하여 보면 간장에 있어서 ACS4는 기본적인 $\beta$-산화뿐만 아니라 호르몬에 의한 조절과 간접적으로는 인슐린에 의한 조절도 받는 것으로 생각되며 다양한 기능을 수행하고 있음을 추측할 수 있다.

Keywords

References

  1. Burton DN, Haavik AG, Porter JW. Comparative studies of the rat and pigeon fatty acid synthetase. Arch Biochem Biophys 126: 141-145, 1968 https://doi.org/10.1016/0003-9861(68)90568-7
  2. Kumar S. Functional deacylases of pigeon liver fatty acid synthetase complex. J Biol Chem 250: 5150-5185, 1975
  3. Suzki H, Kawarabayasi Y, Kondo J, Abe T, NishiKawa K, Kimura S, Hashimoto T, Yamamoto T. Structure and regulation of rat long-chain acyl-CoA synthetase. J Biol Chem 265: 8681-8685, 1990
  4. Fujino T, Yamamoto T. Cloning and functional expression of a novel long-chain acyl-CoA synthetase expressed in brain. J Biochem 111: 197-203, 1992
  5. Fujino T, Kang M, Suzuki H, Iijima H, Yamamoto T. Molecular characterization and expression of rat acyl-CoA synthetase 3. J Biol Chem 271: 16748-16752, 1996 https://doi.org/10.1074/jbc.271.28.16748
  6. Kang MJ, Fujino T, Sasano H, Minekura H, Yabuki N, Nagura H, Iijima H, Ymamoto T. A novel arachidonate-preferring acyl-CoA synthetase is present in steroidogenic cells of the rat adrenal, ovary, and testis. Proc Natl Acad Sci USA 94: 2880-2884, 1997 https://doi.org/10.1073/pnas.94.7.2880
  7. Oikawa E, Iijima H, Suzuki T, Sasano H, Sato H, Kamataki A, Nagura H, Kang MJ, Fujino T, Suzuki H, Yamamoto TT. A novel acyl-CoA synthetase, ACS5, expressed in intestinal epithelial cells and proliferating preadipocytes. J Biochem 124(3): 679-685, 1998 https://doi.org/10.1093/oxfordjournals.jbchem.a022165
  8. Lin L-L, Lin AY, Knopf JL. Cytosolic phospholipase A2 is coupled to hormonally regulated release of arachidonic acid. Proc Natl Acad Sci USA 89: 6147-6151, 1992 https://doi.org/10.1073/pnas.89.13.6147
  9. Lin LL, Wartmann M, Lin AY, Knopf JL, Seth A, Davis RJ. cPLA2 is phosphorylated and activated by MAP kinase. Cell 72(2): 269-278, 1993 https://doi.org/10.1016/0092-8674(93)90666-E
  10. Majerus PW, Prescott SM, Hofmann SL, Neufeld EJ, Wilson DB. Uptake and release of arachidonate by platelets. Adv Prostaglandin Thromboxane Leukot Res 11: 45-52, 1983 https://doi.org/10.1016/0262-1746(83)90108-7
  11. Cho YY, Kang MJ, Sone H, Suzuki T, Abe M, Igarashi M, Tokunaga T, Ogawa S, Takei YA, Miyazawa T, Sasano H, Fujino T, Yamamoto TT. Abnormal uterus with polycysts, accumulation of uterine prostaglandins, and reduced fertility in mice heterozygous for acyl-CoA synthetase 4 deficiency. Biochem Biophys Res Commun 284(4): 993-997, 2001 https://doi.org/10.1006/bbrc.2001.5065
  12. Miyazawa S, Hashimoto T, Yokota S. Identity of long-chain acyl-coenzyme A synthetase of microsomes, mitochondria, and peroxisomes in rat liver. J Biochem 98: 723-733, 1985
  13. Osumi T, Hashimoto T. Enhancement of fatty acyl-CoA oxidizing activity in rat liver peroxisomes by di-(i-ethylhexyl) phthalate. J Biochem 83(5): 1361-1365, 1978
  14. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem 193: 265-275, 1951
  15. Baginski ES, Foa PP, Zak B. Glucose-6-phosphate. In: Methods of enzymatic analysis 2nd English Ed Vol. 2, pp.876-880, Academic press, New York, 1974
  16. Schmidt E. Glutamate dehydrogenase. In: Methods of enzymatic analysis 2nd English Ed Vol. 2, pp.650-656, Academic press, New York, 1974
  17. Abei H. Catalase. In: Methods of enzymatic analysis 2nd English Ed Vol. 2, pp.673-684, Academic press, New York, 1974
  18. Maniatis T, Fritsch EF, Sambrook J. Molecular cloning: A Laboratory Manual (Cold Spring Harbor Lab. Press, Plainview, NY), 2nd Ed. 1989
  19. Lai JC, Sheu KF, Kim YT, Clarke DD, Blass JP. The subcellular localization of glutamate dehydrogenase (GDH): is GDH a marker for mitochondria in brain? Neurochem Res 11: 733-744, 1986 https://doi.org/10.1007/BF00965341
  20. Miyazawa S, Osumi T, Hashimoto T. The presence of a new 3-oxoacyl-CoA thiolase in rat liver peroxisomes. Eur J Biochem 103: 589-596. 1980
  21. Stefan EHA, Fujiki Y, Shio H, Lazarow PB. Partial disassemble of peroxisomes. J Cell Biol 101: 294-305, 1985 https://doi.org/10.1083/jcb.101.1.294
  22. de Duve C, Pressman BC, Glanetto R, Wattiaux R, Appelmans F. Tissue fractionation studies VI. Intracellular distribution patterns of enzymes in rat liver tissue. Biochem J 60: 604-617, 1955
  23. Lewin TM, Kim JH, Granger DA, Vance JE, Coleman RA. Acyl-CoA synthetase isoforms 1, 4, and 5 are present in different subcellular membranes in rat liver and can be inhibited independently. J Biol Chem 276(27): 24674-24679, 2001 https://doi.org/10.1074/jbc.M102036200
  24. Waku K. Origins and fates of fatty acyl-CoA esters. Biochim Biophys Acta 1124(2): 101-111, 1992 https://doi.org/10.1016/0005-2760(92)90085-A
  25. Shimizu T and Wolfe LS. Arachidonic acid cascade and signal transduction. J Neurochem 55: 1-14, 1990 https://doi.org/10.1111/j.1471-4159.1990.tb08813.x
  26. Lippel K. Activation of branched and other long-chain fatty acids by rat liver microsomes. J Lipid Res 14(1): 102-109, 1973
  27. Pande SV, Mead JF. Long chain fatty acid activation in subcellular preparations from rat liver. J Biol Chem 243(2): 352-61, 1968
  28. Iritani N. Nutrition and hormonal regulation of lipogenic-enzyme gene expression in rat liver. Eur J Biochem 205: 433-442, 1992 https://doi.org/10.1111/j.1432-1033.1992.tb16797.x
  29. Girard J, Perdereau D, Foufelle F, Prip-Buus C, Ferre P. Regulation of lipogenic enzyme gene expression by nutrients and hormones. FASEB J 8: 36-42, 1994
  30. Wang H, Walker SW, Mason JI, Morley SD, Williams BC. Role of arachidonic acid metabolism in ACTH-stimulated cortisol secretion by bovine adrenocortical cells. Endocr Res 26: 705-709, 2000 https://doi.org/10.3109/07435800009048590
  31. Wang X and Stocco DM. Cyclic AMP and arachidonic acid: a tale of two pathways. Mol Cell Endocrinol 158: 7-12, 1999 https://doi.org/10.1016/S0303-7207(99)00130-6
  32. Chang LL, Kau MM, Wun WS, Ho LT, Wang PS. Effects of fasting on corticosterone production by zona fasciculata-reticularis cells in ovariectomized rats. J Investig Med 50(2): 86-94, 2002
  33. Cho YY, Kang MJ, Ogawa S, Yamashita Y, Fujino T, Yamamoto TT. Regulation by adrenocorticotropic hormone and arachidonate of the expression of acyl-CoA synthetase 4, an arachidonatepreferring enzyme expressed in steroidogenic tissues. Biochem Biophys Res Commun 274(3): 741-5, 2000 https://doi.org/10.1006/bbrc.2000.3207
  34. Schoonjans K Watanabe M, Suzuki H, Mahfoudi A, Krey G, Wahli W, Grimaldi P, Staaaels B, Yamamoto T, Auwerz J. Induction of the acyl-coenzyme A synthetase gene by fibrates and fatty acids is medicated by a peroxisome proliferator response element in the C promoter. J Biol Chem 270: 19269-19276, 1995 https://doi.org/10.1074/jbc.270.33.19269
  35. Lewin TM, Van Horn CG, Krisans SK, Coleman RA. Rat liver acyl-CoA synthetase 4 is a peripheral-membrane protein located in two distinct subcellular organelles, peroxisomes, and mitochondrial-associated membrane. Arch Biochem Biophys 404(2): 263-270. 2002 https://doi.org/10.1016/S0003-9861(02)00247-3