2005/01/02 by Jin‐ichi Ito, Jin-ichi Ito, Yuko Nagayasu +4 · 8 citations
Immunology and Microbiology · Biochemistry, Genetics and Molecular Biology · Medicine · #Phagocytosis and Immune Regulation #Fibroblast Growth Factor Research #Erythrocyte Function and Pathophysiology
paper · pdf · doi:10.1194/jlr.m400313-jlr200
The astrocytes prepared by 1 week secondary culture after 1 month primary culture of rat brain cells (M/W cells) synthesized and secreted apolipoprotein E (apoE) and cholesterol more than the astrocytes prepared by conventional 1 week primary and 1 week secondary culture (W/W cells) (Ueno, S., J. Ito, Y. Nagayasu, T. Furukawa, and S. Yokoyama. 2002. An acidic fibroblast growth factor-like factor secreted into the brain cell culture medium upregulates apoE synthesis, HDL secretion and cholesterol metabolism in rat astrocytes. Biochim. Biophys. Acta. 1589: 261–272). M/W cells also highly expressed fibroblast growth factor-1 (FGF-1) mRNA. FGF-1 was identified in the cell lysate of both cell types, but M/W cells released more of it into the medium. Immunostaining of FGF-1 and apoE revealed that both localized in the cells that produce glial fibrillary acidic protein. The conditioned media of M/W cells and FGF-1 stimulated W/W cells to release apoE and cholesterol to generate more HDL. Pretreatment with a goat anti-FGF-1 antibody or heparin depleted the stimulatory activity of M/W cell-conditioned medium. The presence of the anti-FGF-1 antibody in the medium suppressed apoE secretion by M/W cells. Differential inhibition of signaling pathways suggested that FGF-1 stimulates apoE synthesis via the phosphoinositide 3-OH kinase for PI3K/Akt pathway. Thus, astrocytes release FGF-1, which promotes apoE-HDL production by an autocrine mechanism.These results are consistent with our in vivo observation that astrocytes produce FGF-1 before the increase of apoE in the postinjury lesion of the mouse brain (Tada, T., J. Ito, M. Asai, and S. Yokoyama. 2004. Fibroblast growth factor 1 is produced prior to apolipoprotein E in the astrocytes after cryo-injury of mouse brain. Neurochem. Int. 45: 23–30). The astrocytes prepared by 1 week secondary culture after 1 month primary culture of rat brain cells (M/W cells) synthesized and secreted apolipoprotein E (apoE) and cholesterol more than the astrocytes prepared by conventional 1 week primary and 1 week secondary culture (W/W cells) (Ueno, S., J. Ito, Y. Nagayasu, T. Furukawa, and S. Yokoyama. 2002. An acidic fibroblast growth factor-like factor secreted into the brain cell culture medium upregulates apoE synthesis, HDL secretion and cholesterol metabolism in rat astrocytes. Biochim. Biophys. Acta. 1589: 261–272). M/W cells also highly expressed fibroblast growth factor-1 (FGF-1) mRNA. FGF-1 was identified in the cell lysate of both cell types, but M/W cells released more of it into the medium. Immunostaining of FGF-1 and apoE revealed that both localized in the cells that produce glial fibrillary acidic protein. The conditioned media of M/W cells and FGF-1 stimulated W/W cells to release apoE and cholesterol to generate more HDL. Pretreatment with a goat anti-FGF-1 antibody or heparin depleted the stimulatory activity of M/W cell-conditioned medium. The presence of the anti-FGF-1 antibody in the medium suppressed apoE secretion by M/W cells. Differential inhibition of signaling pathways suggested that FGF-1 stimulates apoE synthesis via the phosphoinositide 3-OH kinase for PI3K/Akt pathway. Thus, astrocytes release FGF-1, which promotes apoE-HDL production by an autocrine mechanism. These results are consistent with our in vivo observation that astrocytes produce FGF-1 before the increase of apoE in the postinjury lesion of the mouse brain (Tada, T., J. Ito, M. Asai, and S. Yokoyama. 2004. Fibroblast growth factor 1 is produced prior to apolipoprotein E in the astrocytes after cryo-injury of mouse brain. Neurochem. Int. 45: 23–30). The brain cells are segregated from lipoproteins in the systemic circulation by the blood-brain barrier, so that cholesterol homeostasis in the brain is dependent on its specific extracellular lipid transport system by apolipoproteins and lipoproteins (1Chiba H. Mitamura T. Fujisawa S. Ogata A. Aimoto Y. Tashiro K. Kobayashi K.K. Apolipoproteins in rat cerebrospinal fluid: a comparison with plasma lipoprotein metabolism and effect of aging.Neurosci. Lett. 1991; 133: 207-210Crossref PubMed Scopus (23) Google Scholar, 2Bjorkhem I. Lutjohann D. Breuer O. Sakinis A. Wennmalm A. Importance of a novel oxidative mechanism for elimination of brain cholesterol.J. Biol. Chem. 1997; 272: 30178-30184Abstract Full Text Full Text PDF PubMed Scopus (240) Google Scholar, 3Bjorkhem I. Lutjohann D. Diczfalusy U. Stahle L. Ahlborg G. Wahren J.J. Cholesterol homeostasis in human brain: turnover of 24S-hydroxycholesterol and evidence for a cerebral origin of most of this oxysterol in the circulation.J. 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Purification and characterization of astrocytes-secreted apolipoprotein E and J-containing lipoproteins from wild-type and human apoE transgenic mice.Neurochem. Int. 2001; 39: 415-425Crossref PubMed Scopus (130) Google Scholar). The phenotype of human brain apoE does not change after liver transplantation, so that brain apoE is mostly produced in the brain (11Linton M.F. Gish R. Hubl S.T. Butler E. Esquivel C. Bry W.L. Boyles J.K. Wardell M.R. Young S.G.G. Phenotypes of apolipoprotein B and E after liver transplantation.J. Clin. Invest. 1991; 88: 270-281Crossref PubMed Scopus (285) Google Scholar). It is known that apoE is produced mainly by astrocytes and partly by microglia in the brain, suggesting that astrocytes play an important role in cholesterol homeostasis in the central nervous system (5Ito J. Yokoyama S. Roles of glia cells in cholesterol homeostasis in the brain.Adv. Mol. Cell Biol. 2004; 31: 519-534Crossref Scopus (15) Google Scholar, 10DeMattos B.R. Brendza P.R. Heuser E.J. Kierson M. Cirrito R.J. Fryer L. Sullivan M.P. Fagan M.A. Han X. Holtzman M.D.D. Purification and characterization of astrocytes-secreted apolipoprotein E and J-containing lipoproteins from wild-type and human apoE transgenic mice.Neurochem. Int. 2001; 39: 415-425Crossref PubMed Scopus (130) Google Scholar, 12Pitas R.E. Boyles J.K. Lee S.H. Foss D. Mahley R.W.W. Astrocytes synthesize apolipoprotein E and metabolize apolipoprotein E-containing lipoproteins.Biochim. Biophys. Acta. 1987; 917: 148-161Crossref PubMed Scopus (569) Google Scholar, 13Boyles J.K. Pitas R.E. Wilson E. Mahley R.W. Taylor J.M.M. Apolipoprotein E associated with astrocytic glia of the central nervous system and with nonmyelinating glia of the peripheral nervous system.J. Clin. Invest. 1985; 76: 1501-1513Crossref PubMed Scopus (651) Google Scholar, 14Nakai M. Kawamata T. Taniguchi T. Maeda K. Tanaka C. Expression of apolipoprotein E mRNA in rat microglia.Neurosci. 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Differential generation of high-density lipoprotein by endogenous and exogenous apolipoproteins in cultured fetal rat astrocytes.J. Neurochem. 1999; 72: 2362-2369Crossref PubMed Scopus (65) Google Scholar). They also react with exogenous apoA-I to generate cholesterol-poor HDL through a unique system for intracellular cholesterol transport (18Ito J. Nagayasu Y. Yokoyama S. Cholesterol-sphingomyelin interaction in membrane and apolipoprotein-mediated cellular cholesterol efflux.J. Lipid Res. 2000; 41: 894-904Abstract Full Text Full Text PDF PubMed Google Scholar, 19Ito J. Nagayasu Y. Ueno S. Yokoyama S. Apolipoprotein-mediated cellular lipid release requires replenishment of sphingomyelin in a phosphatidylcholine-specific phospholipase C-dependent manner.J. Biol. Chem. 2002; 277: 44709-44714Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar, 20Ito J. Nagayasu Y. Kato K. Sato R. Yokoyama S. Apolipoprotein A-I induces translocation of cholesterol, phospholipid, and caveolin-1 to cytosol in rat astrocytes.J. Biol. Chem. 2002; 277: 7929-7935Abstract Full Text Full Text PDF PubMed Scopus (67) Google Scholar). Like plasma HDL, ATP binding cassette transporter A1 supports such production of brain HDL, although other pathways may also function as backup systems (21Wahrle S.E. Jiang H. M. J. Han X. Fryer T. Holtzman D.M.M. is for normal central nervous system apoE and for of Biol. Chem. 2004; Full Text Full Text PDF PubMed Scopus Google Scholar, S. L. M.R. of apolipoprotein E metabolism in Biol. Chem. 2004; Full Text Full Text PDF PubMed Scopus Google Scholar). These lipoproteins are to play important in lipid transport in the brain. It been that apoE synthesis is in the brain and after J.K. Pitas R.E. Wilson E. Mahley R.W. Taylor J.M.M. Apolipoprotein E associated with astrocytic glia of the central nervous system and with nonmyelinating glia of the peripheral nervous system.J. Clin. Invest. 1985; 76: 1501-1513Crossref PubMed Scopus (651) Google Scholar, that in but not in 1985; PubMed Scopus Google Scholar, N. of rat E and A-I apolipoproteins and optic nerve Biol. Chem. Full Text PDF PubMed Google Scholar, M.J. Mahley R.W. Expression of apolipoprotein E nerve and PubMed Scopus Google Scholar, J.J. stimulates the secretion of apolipoprotein E by PubMed Scopus Google Scholar, R.W. Apolipoprotein cholesterol transport with role in cell PubMed Scopus Google Scholar, A. M. M. A. nerve in and apolipoprotein Neurochem. PubMed Scopus Google Scholar, K. Apolipoprotein E and the of the brain to 1999; PubMed Scopus Google Scholar, A. D. apolipoprotein E with the of in the of Lett. 2002; PubMed Scopus Google Scholar, K. T. N. A. K. Tsuchiya K. of apolipoprotein E in human brain with cerebral PubMed Scopus Google and this is to in the of the H. Apolipoprotein have to cerebral 1997; PubMed Scopus Google Scholar, K. Apolipoprotein E and the to 1998; PubMed Scopus Google Scholar, H. M. Apolipoprotein E from cerebral in the 1999; PubMed Scopus Google Scholar, G. S. M. J. D. A. D.M.M. but not astrocyte in apoE 12: PubMed Scopus Google Scholar). of apoE binding are identified in the brain: lipoprotein lipoprotein lipoprotein and apoE apoE is to function as a of lipoproteins for lipid brain cells G. M.J. Expression and function of the lipoprotein in central Biol. Chem. Full Text PDF PubMed Google Scholar, J. Schneider cholesterol transport to lipoprotein lipoprotein and apolipoprotein E Biophys. Acta. 2000; PubMed Scopus Google Scholar). of are also to for the of brain cells the of the brain J. The in the 2001; Full Text Full Text PDF PubMed Scopus Google Scholar). that astrocytes prepared by 1 month primary culture of rat fetal brain cells and 1 week secondary culture (M/W cells) synthesized and secreted apoE and cholesterol more than astrocytes prepared to the conventional of 1 week primary and 1 week secondary culture (W/W cells) S. J. Nagayasu Y. T. Yokoyama S. An acidic fibroblast growth factor-like factor secreted into the brain cell culture medium upregulates apoE synthesis, HDL secretion and cholesterol metabolism in rat Biophys. Acta. 2002; 1589: PubMed Scopus Google Scholar). fibroblast growth factor-1 factor is secreted by the rat fetal brain cells, and conditioned media stimulated W/W astrocytes for the secretion of also found that FGF-1 is produced by astrocytes to the of mouse brain before the increase of apoE synthesis in vivo T. J. Asai M. Yokoyama S. Fibroblast growth factor 1 is produced prior to apolipoprotein E in the astrocytes after cryo-injury of mouse Int. 2004; 45: PubMed Scopus Google Scholar). identified a of FGF-1 to for H. Y. H. K. J. Yokoyama S. T. K. T. in fibroblast growth factor 1 of Biophys. Res. 2004; PubMed Scopus Google Scholar). Thus, that FGF-1 is a of apoE synthesis and generation of HDL in the postinjury brain, by an autocrine mechanism. the to the cells that FGF-1 in the culture system and an autocrine mechanism for this factor to apoE-HDL is an important to the mechanism for the production of apoE and its HDL in the postinjury brain for from Astrocytes prepared from the fetal brain of to the R. K. effect of brain and on brain cells in Cell Res. PubMed Scopus Google Scholar). of the the brain was into and with in for The cell by for was cultured in medium fetal for as a primary with 1 the cells cultured in for 1 week as a secondary culture (M/W astrocytes prepared by a conventional of 1 week primary and 1 week secondary culture (W/W astrocytes fibrillary acidic and S. J. Nagayasu Y. T. Yokoyama S. An acidic fibroblast growth factor-like factor secreted into the brain cell culture medium upregulates apoE synthesis, HDL secretion and cholesterol metabolism in rat Biophys. Acta. 2002; 1589: PubMed Scopus Google Scholar). astrocytes a with four and in for The cells with in for of the the cells with and in in the presence of 1 Cholesterol was from the cells and the conditioned medium with and and by on in the cholesterol was H. Yokoyama S. of apolipoprotein with of lipoproteins and of cellular cholesterol.J. Biol. Chem. 1991; Full Text PDF PubMed Google Scholar). The medium was also by as J-i. Zhang Y.L. Asai M. Yokoyama S. Differential generation of high-density lipoprotein by endogenous and exogenous apolipoproteins in cultured fetal rat astrocytes.J. Neurochem. 1999; 72: 2362-2369Crossref PubMed Scopus (65) Google Scholar). cell by the medium was on the and 1 for and for cholesterol by the S. S. Y. H. Yokoyama Characterization of apolipoprotein-mediated HDL generation by in a cell 2000; 39: PubMed Scopus Google and for apoE by The cells with a after four with The cell by for was with and the for with for The was for for of and cell The was and for to as a cell Cell was from the conditioned medium by for in the cell or in the conditioned medium was by and for by and to a membrane The membrane was with a goat anti-FGF-1 antibody and a antibody rat a from of cellular was from rat astrocytes with and to generate in a The was to the for rat apoE mRNA and FGF-1 mRNA as in the S. J. Nagayasu Y. T. Yokoyama S. An acidic fibroblast growth factor-like factor secreted into the brain cell culture medium upregulates apoE synthesis, HDL secretion and cholesterol metabolism in rat Biophys. Acta. 2002; 1589: PubMed Scopus Google Scholar). of the an was with prepared The was by an The apoE and The FGF-1 and Astrocytes on a culture with and with for The cells with in for after with The cells with with goat anti-FGF-1 or apoE for and with or antibody for the cells with for and The cells by with for M/W astrocytes after in of and for with the cells with goat anti-FGF-1 or goat apoE antibody and mouse antibody in and for 1 The cells with antibody or antibody in the presence of or for 1 after with The cells by the of the to apoE synthesis, rat astrocytes (W/W cells) with and for with FGF-1 in the presence or of an of phosphoinositide 3-OH kinase for or an of The cells in the in for and in for after The conditioned medium was for to cell with and for The was by and apoE of by FGF-1 was also the cells with FGF-1 in for the cytosol was prepared as a of the cell in for with of and for The cytosol with was by and mouse kinase B antibody and antibody culture of the rat brain cells, a of identified 1 and astrocytes after identified Expression of the FGF-1 was not 1 week primary culture and was after These that FGF-1 was produced by astrocytes than the primary culture of brain cells. the cells that produce FGF-1 and apoE more was for FGF-1 and apoE in astrocyte by 1 week secondary culture after primary culture of the brain cells for and The increase of FGF-1 and apoE was in cells prepared after primary culture for both and the astrocyte of week primary and 1 week secondary culture (M/W a of cells found with an of cells. also identified in cells M/W cells by to that both FGF-1 and apoE produced by astrocytes. that FGF-1 and apoE both identified in the cells. M/W cells for the production and secretion of The conditioned media of the brain cell primary culture and of the astrocyte for on the astrocytes prepared by a conventional of 1 week primary and 1 week secondary culture (W/W cells) The medium of the primary culture for and and that of M/W cells stimulated apoE secretion from W/W cells The astrocytes after 1 week primary and week secondary culture cells) also the conditioned medium to apoE of cholesterol release from W/W cells by M/W cell-conditioned medium was by of the medium with anti-FGF-1 and with is consistent with the results with the conditioned medium of brain cells S. J. Nagayasu Y. T. Yokoyama S. An acidic fibroblast growth factor-like factor secreted into the brain cell culture medium upregulates apoE synthesis, HDL secretion and cholesterol metabolism in rat Biophys. Acta. 2002; 1589: PubMed Scopus Google activity in conditioned The effect of the conditioned media of the brain cells and astrocytes on the secretion of apoE by W/W cells. The conditioned media prepared from the primary culture for cell and of W/W cells and from M/W cells and cells prepared by 1 week primary and week secondary culture W/W cells with conditioned medium in 1 of culture for and with the cultured medium was by for of with anti-FGF-1 antibody or heparin of the conditioned medium of M/W cells on its stimulatory on W/W cells for the release of M/W cell conditioned the medium with normal goat anti-FGF-1 for W/W cells with or of or for and by with in 1 of for with the cells for in The lipid from the conditioned medium was by to in the and of The effect of FGF-1 was in the in of the medium revealed an increase of HDL production by astrocytes (W/W cells) stimulated by FGF-1 was of the of HDL with this the of apoE in the The increase of apoE by FGF-1 was with the cholesterol of apoE-HDL production by rat astrocytes stimulated by astrocytes with or FGF-1 for and and the conditioned medium was by after of cell as in the Cholesterol was as in the with the conditioned medium FGF-1, and with the conditioned medium with the of the The for apoE by as in the The and of FGF-1 in M/W astrocytes M/W cells expressed a of FGF-1 mRNA than W/W cells the other a of FGF-1 was as a in the of the of both W/W and M/W cells by an anti-FGF-1 antibody a of this was secreted into the culture medium by M/W cells than by W/W cells, as identified by with anti-FGF-1 antibody secretion of apoE by M/W cell was the cells to an anti-FGF-1 antibody the Thus, that M/W astrocytes produce and FGF-1 and that the secreted FGF-1 stimulates the cells to produce and apoE by an autocrine mechanism. pathways for the of apoE synthesis by FGF-1 The increase of apoE secretion by FGF-1 was suppressed by a PI3K/Akt but not by a of in cytosol was in by FGF-1 Thus, FGF-1 stimulates apoE synthesis via the PI3K/Akt than by the pathway. that factor is secreted by week primary cultured rat brain cells into the culture medium and the production and secretion of apoE and in W/W cells S. J. Nagayasu Y. T. Yokoyama S. An acidic fibroblast growth factor-like factor secreted into the brain cell culture medium upregulates apoE synthesis, HDL secretion and cholesterol metabolism in rat Biophys. Acta. 2002; 1589: PubMed Scopus Google Scholar). also in vivo that FGF-1 is produced before the production of apoE in astrocytes after of the mouse brain T. J. Asai M. Yokoyama S. Fibroblast growth factor 1 is produced prior to apolipoprotein E in the astrocytes after cryo-injury of mouse Int. 2004; 45: PubMed Scopus Google Scholar). that FGF-1 is of the for the production and release of apoE and apoE-HDL in astrocytes after brain and that it is released by astrocytes to this in an autocrine the this in to that astrocytes are in of FGF-1 and apoE-HDL The results to that M/W astrocytes release FGF-1 and the production of apoE-HDL by an autocrine The astrocytes prepared by 1 month primary and 1 week secondary culture of rat fetal brain cells (M/W cells) expressed FGF-1 mRNA and synthesized and released FGF-1 into the conditioned identified as a heparin binding and anti-FGF-1 of M/W cells synthesized and secreted apoE with the cellular lipid to generate a of and this was suppressed by the presence of an anti-FGF-1 antibody in the medium the The conditioned medium of M/W cells stimulated apoE synthesis in the astrocytes (W/W and this activity was by of the medium with an anti-FGF-1 The cells that produce FGF-1 and apoE both from the of signaling pathways suggested that FGF-1 stimulates apoE synthesis via PI3K/Akt the for the of apoE synthesis and secretion in human growth factor stimulated apoE and and not F. 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