Formation of lipid droplets induced by 2,3-dihydrogeranylgeranoic acid distinct from geranylgeranoic acid

• Authors: Yuichi Kodaira , Takeru Kusumoto , Takeshi Takahashi , Yoshihiro Matsumura , Yukino Miyagi , Kyoko Okamoto , Yoshihiro Shidoji , Hiroshi Sagami
• Languages of publication: EN

Abstracts

EN

Geranylgeranoic acid (GGA) and 2,3-dihydrogeranylgeranoic acid (2,3-diGGA) are geranylgeraniol-derived metabolites (Kodaira et al. (2002) J Biochem 132: 327-334). In the present study, we examined the effects of these acids on HL-60 cells. The cells were differentiated into neutrophils by GGA stimulation like retinoic acid stimulation. In the case of cells stimulated with 2,3-diGGA, neutrophils were not detected, but the formation of lipid droplets was induced. On the other hand, when the cells were cultured in the presence of 0.1% FBS instead of 10% FBS, apoptotic cells were induced not only by GGA stimulation but also with 2,3-diGGA. In the latter case, when the cells were cultured in the co-presence of a caspase-3 inhibitor (Ac-DMQD-CHO), the lipid droplets formation was observed in the cells. These results suggest that GGA and 2,3-diGGA are extremely different from each other with respect to their effects on HL-60 cells.

Keywords

EN

lipid droplets; geranylgeranoic acid; 2,3-dihydrogeranylgeranoic acid; HL-60; neutrophils

• Publisher: Polish Biochemical Society
• Journal: Acta Biochimica Polonica
• Year: 2007
• Volume: 54
• Issue: 4
• Pages: 777-782

Dates

published

2007

received

2007-08-08

revised

2007-11-22

accepted

2007-12-03

(unknown)

2007-12-10

Contributors

author

Yuichi Kodaira

• Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, Sendai, Japan

author

Takeru Kusumoto

• Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, Sendai, Japan

author

Takeshi Takahashi

• Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, Sendai, Japan

author

Yoshihiro Matsumura

• Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, Sendai, Japan

author

Yukino Miyagi

• Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, Sendai, Japan

author

Kyoko Okamoto

• Molecular and Cellular Biology, Graduate School of Human Health Sciences, Siebold University of Nagasaki, Nagasaki, Japan

author

Yoshihiro Shidoji

• Molecular and Cellular Biology, Graduate School of Human Health Sciences, Siebold University of Nagasaki, Nagasaki, Japan

author

Hiroshi Sagami

• Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, Sendai, Japan

References

• Appella DH, Moritani Y, Shintani R, Ferreira EM, Buchwald SL (1999) Asymmetric conjugate reduction of α,β-unsaturated esters using a chiral phosphine-copper catalyst.J Am Chem Soc 121: 9473-9474.
• Araki H, Shidoji Y, Yamada Y, Moriwaki H, Muto Y (1995) Retinoid agonist activities of synthesis geranylgeranoic acid derivatives. Biochem Biophys Res Commun 209: 66-72.
• Bligh EG, Dyer WJ (1959) A rapid method of total lipid extraction and purification. Can J Biochem Physiol 37: 911-917.
• Breitman TR, Selonick SE, Collins SJ (1980) Induction of differentiation of the human promyelocytic leukemia cell line. Proc Natl Acad Sci USA 77: 2936-2940.
• Christophe J, Popjak G (1964) Studies on the biosynthesis of cholesterol: XIV the origin of prenoic acids from allyl pyrophosphates in liver enzyme systems. J Lipid Res 2: 244-257.
• Crick DC, Andres DA, Waechter CD (1997) Pathway utilizing farnesol and geranylgeraniol for protein isoprenylation. Biochem Biophys Res Commun 237: 483-487.
• Dituri F, Rabinowitz JL, Hullin RP, Gurin S (1957) Precusors of squalene and cholesterol. J Biol Chem 229: 825-836.
• Fliesler SJ, Schroepfer GJ (1983) Metabolism of mevalonic acid in cell-free homogenates of bovine retinas. Formation of novel isoprenoid acids. J Biol Chem 258: 15062-15070.
• Forman BM, Ruan B, Chen J, Schroepfer GJ, Evans RM (1997) The orphan nuclear receptor LXRα is positively and negatively regulated by distinct products of mevalonate metabolism. Proc Natl Acad Sci USA 94: 10588-10593.
• Goldstein JL, Brown MS (1990) Regulation of the mevalonate pathway. Nature 343: 425-430.
• Gonzalez-Pacanowska D, Arison B, Havel CM, Watson JA (1988) Isopentenoid synthesis in isolated embryonic Drosophila cells. Farnesol catabolism and ω-oxidation. J Biol Chem 263: 1301-1306.
• Healy DA, Watson RWG, Newsholme P (2003) Polyunsaturated and monounsaturated fatty acids increase neutral lipid accumulation caspase activation and apoptosis in a neutrophil-like differentiated HL-60 cell line. Clin Sci 104: 171-179.
• Kodaira Y, Usui K, Kon I, Sagami H (2002) Formation of (R)-2,3-dihydrogeranylgeranoic acid from geranylgeraniol in rat thymotcytes. J Biochem 132: 327-334.
• Morjani H, Aouali N, Belhoussine R, Veldman RJ, Levade T, Manfait M (2001) Elevation of glucosylceramide in multidrug-resistant cancer cells and accumulation in cytoplasmic droplets. Int J Cancer 94: 157-165.
• Popjak G (1959) The biosynthesis of derivatives of allylic alcohols from [2-^14C]mevalonate in liver enzyme preparations and their relation to synthesis of squalene. Tetrahedron Lett 19-28.
• Shidoji Y, Nakamura N, Moriwaki H, Muto Y (1997) Rapid loss in the mitochondorial membrane potential during geranylgeranoic acid-induced apoptosis. Biochem Biophys Res Commun 230: 58-63.
• Shimabukuro M, Zhou Y-T, Levi M, Unger RH (1998) Fatty acid-induced β cell apoptosis: a link between obesity and diabetes. Proc Natl Acad Sci USA 95: 2498-2502.
• Wang X, Wu J, Shidoji Y, Muto Y, Ohishi N, Yagi K, Ikegamo S, Shinki T, Udagawa N, Suda T, Ishimi Y (2002) Effects of geranylgeranoic acid in bone: induction of osteoblast differentiation and inhibition of osteoclast formation. J Bone Miner Res 17: 91-100.
• Wolfrum C, Borrmann CM, Borchers T, Spener F (2001) Fatty acids and hypolipidemic drugs regulate peroxisome proliferator-activated receptors α- and γ-mediated gene expression via liver fatty acid binding protein: a signaling path to the nucleus. Proc Natl Acad Sci USA 98: 2323-2328.
• Yamakawa-Karakida N, Sugita K, Inukai T, Goi K, Nakamura M, Uno K, Sato H, Kagami K, Barker N, Nakazawa S (2002) Ligand activation of peroxisome proliferators-activated receptor gamma induces apoptosis of leukemia cells by down-regulating the c-myc gene expression via blockade of Tcf-4 activity. Cell Death Differ 9: 513-526.