Chiaki Ikegami
Osaka University
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Publication
Featured researches published by Chiaki Ikegami.
Journal of Lipid Research | 2007
Masahiro Koseki; Ken-ichi Hirano; Daisaku Masuda; Chiaki Ikegami; Masaki Tanaka; Akemi Ota; Jose C. Sandoval; Yumiko Nakagawa-Toyama; Satoshi B. Sato; Toshihide Kobayashi; Yukiko Shimada; Yoshiko Ohno-Iwashita; Fumihiko Matsuura; Iichiro Shimomura; Shizuya Yamashita
Lipid rafts on the cell surface are believed to be very important as platforms for various cellular functions. The aim of this study was to know whether defective lipid efflux may influence lipid rafts on the cell surface and their related cellular functions. We investigated macrophages with defective lipid efflux from ATP binding cassette transporter A1-deficient (Abca1-KO) mice. Lipid rafts were evaluated by the following two novel probes: a biotinylated and protease (subtilisin Carlsberg)-nicked derivative of 𝛉-toxin and a fluorescein ester of polyethylene glycol-derived cholesterol. Lipid rafts in Abca1-KO macrophages were increased, as demonstrated by both probes. Moreover, activities of nuclear factor κB, mRNA and intracellular distribution, and secretion of tumor necrosis factor-α (TNF-α) were examined after stimulation by lipopolysaccharides (LPSs). LPS-induced responses of the activation of nuclear factor κB and TNF-α were more prompt and accelerated in the Abca1-KO macrophages compared with wild-type macrophages. Modification of lipid rafts by cyclodextrin and nystatin corrected the abnormal response, suggesting an association between the increased lipid rafts and abnormal TNF-α secretion. We report here that Abca1-KO macrophages with defective lipid efflux exhibited increased lipid rafts on the cell surface and accelerated TNF-α secretion.
Biochemical and Biophysical Research Communications | 2002
Tohru Ohama; Kenichi Hirano; Zhongyan Zhang; Ryo Aoki; Kenichi Tsujii; Yumiko Nakagawa-Toyama; Kosuke Tsukamoto; Chiaki Ikegami; Akifumi Matsuyama; Masato Ishigami; Naohiko Sakai; Hisatoyo Hiraoka; Kazumitsu Ueda; Shizuya Yamashita; Yuji Matsuzawa
ATP-binding cassette transporter-1 (ABCA1) is a cause of Tangier disease, which is a familial deficiency of plasma high density lipoproteins (HDL). This molecule is known to be expressed in the multiple tissues and organs including small intestines, liver, and macrophages in the blood vessels. Recent in vivo studies suggested that ABCA1 plays some roles in the flux of cholesterol in the intestines. One of the major questions to understand the roles of ABCA1 in the intestines is the expression pattern in the intestinal epithelial cells. To address this issue, we have investigated the expression and regulation of ABCA1 in Caco-2 cells cultured on Transwell as a model, especially focusing on possible polarized expression of ABCA1. The expression of ABCA1 was up-regulated during the differentiation and under the stimulation of LXR/RXR by the addition of 9-cis-retinoic acid (9-cis-RA) and 22-R-hydroxycholesterol (22-OH). Apolipoprotein-AI-mediated cholesterol efflux was dominant toward the basolateral side of polarized cells when stimulated by 9-cis-RA and 22-OH. The cell surface biotinylation experiment followed by Western blot analyses demonstrated a markedly dominant expression of ABCA1 on the basolateral surface, which was clearly confirmed by the confocal laser scanning microscopy. In conclusion, the present study demonstrates that ABCA1 is dominantly expressed on the basolateral surface of Caco-2 cells tested, suggesting that this molecule may play a role in the basolateral movement of cholesterol at least when stimulated by LXR/RXR ligands.
Arteriosclerosis, Thrombosis, and Vascular Biology | 2002
Kosuke Tsukamoto; Ken-ichi Hirano; Shizuya Yamashita; Naohiko Sakai; Chiaki Ikegami; Zhongyan Zhang; Fumihiko Matsuura; Hisatoyo Hiraoka; Akifumi Matsuyama; Masato Ishigami; Yuji Matsuzawa
Objective—Many cell types in atherosclerotic lesions are thought to have various biological abnormalities, such as impaired lipid homeostasis and slow cell proliferation, which may be related to senescence at cellular and individual levels. One of the common characteristics of senescent cells in vitro is the alteration of actin cytoskeletons, which have been reported to be involved in the intracellular transport of lipids. Recently, we raised the hypothesis that Cdc42, which is a member of the Rho-GTPase family and is known to play an important role in actin dynamics, might be important in cellular lipid transport. Methods and Results—In the present study, we found that the protein expression levels and GTP-binding activities of Cdc42 were decreased in aged human skin fibroblasts. Moreover, we found the intracellular kinetics of Golgi-associated lipids to be retarded in these cells, which was demonstrated by the fluorescence recovery after photobleaching (FRAP) technique and the use of N-[7-(4-nitrobenzo-2-oxa-1,3-diazole)]-6-aminohexanoyl-d-erythro-sphingosine as a tracer. To correlate the decreased expression of Cdc42 with the retarded FRAP, we complemented the amount of wild-type c-myc–tagged Cdc42Hs (myc-Cdc42Hs-WT) by adenovirus-mediated gene transfer. We further tested the effect of the dominant-active form (myc-Cdc42Hs-DA, V12Cdc42Hs) or dominant-negative form (myc-Cdc42Hs-DN, N17Cdc42Hs) of Cdc42Hs on FRAP. Introduction of myc-Cdc42Hs-WT or myc-Cdc42Hs-DA recovered the retarded FRAP in the aged fibroblasts. Conversely, control fibroblasts infected with myc-Cdc42Hs-DN exhibited significantly retarded FRAP. Conclusions—These data clearly indicate that the expression of Cdc42, a small G protein, is decreased in the aged cells in close association with the retarded intracellular lipid transport. The present study demonstrates a possible function of Cdc42 in the mediation of intracellular lipid transport.
Experimental Gerontology | 2005
Zhongyan Zhang; Ken-ichi Hirano; Kosuke Tsukamoto; Chiaki Ikegami; Masahiro Koseki; Kaoru Saijo; Tadao Ohno; Naohiko Sakai; Hisatoyo Hiraoka; Iichiro Shimomura; Shizuya Yamashita
Werner syndrome (WS) is characterized by the early onset of senescent phenotypes including premature atherosclerotic cardiovascular diseases, although the underlying molecular mechanism for atherosclerosis has not been fully understood yet. Cholesterol efflux from the cells is the initial step of reverse cholesterol transport, a major protective system against atherosclerosis. The aim of the present study was to determine whether this crucial step may be altered in WS. We examined intracellular lipid transport and cholesterol efflux and the expression levels of its related molecules in skin fibroblasts obtained from patients with WS. Cholesterol efflux was markedly reduced in the WS fibroblasts in association with increased cellular cholesterol. Fluorescent recovery after photobleaching (FRAP) technique revealed that intracellular lipid transport around Golgi apparatus was markedly reduced when using a C6-NBD-Ceramide as a tracer. Cdc42 protein and its GTP-bound form were markedly reduced in the WS fibroblasts. The complementation of wild-type Cdc42 corrected cholesterol efflux, intracellular lipid transport, and cellular cholesterol levels in the WS fibroblasts. These data indicated that the reduced expression of Cdc42 may be responsible for the abnormal lipid transport, which in turn might be related to the cardiovascular manifestations in WS.
Biochemical and Biophysical Research Communications | 2001
Kosuke Tsukamoto; Kenichi Hirano; Kenichi Tsujii; Chiaki Ikegami; Zhang Zhongyan; Yoshiharu Nishida; Tohru Ohama; Fumihiko Matsuura; Shizuya Yamashita; Yuji Matsuzawa
Biochemical and Biophysical Research Communications | 2002
Yoshiharu Nishida; Kenichi Hirano; Kosuke Tsukamoto; Makoto Nagano; Chiaki Ikegami; Kirsten Roomp; Mitsuaki Ishihara; Naoki Sakane; Zhongyan Zhang; Kenichi Tsujii; Akifumi Matsuyama; Tohru Ohama; Fumihiko Matsuura; Masato Ishigami; Naohiko Sakai; Hisatoyo Hiraoka; Hiroaki Hattori; Cheryl L. Wellington; Yoshihide Yoshida; Susumu Misugi; Michael R. Hayden; Toru Egashira; Shizuya Yamashita; Yuji Matsuzawa
Biochemical and Biophysical Research Communications | 2007
Fumihiko Matsuura; Ken-ichi Hirano; Chiaki Ikegami; Jose C. Sandoval; Hiroyuki Oku; Miyako Yuasa-Kawase; Kazumi Tsubakio-Yamamoto; Masahiro Koseki; Daisaku Masuda; Kenichi Tsujii; Masato Ishigami; Makoto Nishida; Iichiro Shimomura; Masatsugu Hori; Shizuya Yamashita
Japanese Circulation Journal-english Edition | 2006
Masahiro Koseki; Ken-ichi Hirano; Daisaku Masuda; Chiaki Ikegami; Yumiko Toyama; yukiko shimada; Yoshikko Iwashita; Iichiro Shimomura; Shizuya Yamashita; Masatsugu Hori
Japanese Circulation Journal-english Edition | 2006
Daisaku Masuda; Ken-ichi Hirano; Yumiko Toyama; Masahiro Koseki; Chiaki Ikegami; Mitsukazu Yamane; Iichiro Shimomura; Shizuya Yamashita; Masatsugu Hori
Japanese Circulation Journal-english Edition | 2006
Ken-ichi Hirano; Yumiko Nakagawa-Toyama; Chiaki Ikegami; Kosuke Tsukamoto; Masahiro Koseki; Daisaku Masuda; Motohiro Kirino; Makoto Nishida; Shizuya Yamashita; Masatsugu Hori