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971.
Seiji Nakamura Toshinari Takamura Naoto Matsuzawa-Nagata Hiroaki Takayama Hirofumi Misu Hiroyo Noda Satoko Nabemoto Seiichiro Kurita Tsuguhito Ota Hitoshi Ando Ken-ichi Miyamoto Shuichi Kaneko 《The Journal of biological chemistry》2009,284(22):14809-14818
Visceral adiposity in obesity causes excessive free fatty acid (FFA) flux
into the liver via the portal vein and may cause fatty liver disease and
hepatic insulin resistance. However, because animal models of insulin
resistance induced by lipid infusion or a high fat diet are complex and may be
accompanied by alterations not restricted to the liver, it is difficult to
determine the contribution of FFAs to hepatic insulin resistance. Therefore,
we treated H4IIEC3 cells, a rat hepatocyte cell line, with a monounsaturated
fatty acid (oleate) and a saturated fatty acid (palmitate) to investigate the
direct and initial effects of FFAs on hepatocytes. We show that palmitate, but
not oleate, inhibited insulin-stimulated tyrosine phosphorylation of insulin
receptor substrate 2 and serine phosphorylation of Akt, through c-Jun
NH2-terminal kinase (JNK) activation. Among the well established
stimuli for JNK activation, reactive oxygen species (ROS) played a causal role
in palmitate-induced JNK activation. In addition, etomoxir, an inhibitor of
carnitine palmitoyltransferase-1, which is the rate-limiting enzyme in
mitochondrial fatty acid β-oxidation, as well as inhibitors of the
mitochondrial respiratory chain complex (thenoyltrifluoroacetone and carbonyl
cyanide m-chlorophenylhydrazone) decreased palmitate-induced ROS
production. Together, our findings in hepatocytes indicate that palmitate
inhibited insulin signal transduction through JNK activation and that
accelerated β-oxidation of palmitate caused excess electron flux in the
mitochondrial respiratory chain, resulting in increased ROS generation. Thus,
mitochondria-derived ROS induced by palmitate may be major contributors to JNK
activation and cellular insulin resistance.Insulin is the major hormone that inhibits gluconeogenesis in the liver.
Visceral adiposity in obesity causes hepatic steatosis and insulin resistance.
In an insulin-resistant state, impaired insulin action allows enhancement of
glucose production in the liver, resulting in systemic hyperglycemia
(1) and contributing to the
development of type 2 diabetes. In addition, we have demonstrated
experimentally that insulin resistance accelerated the pathology of
steatohepatitis in genetically obese diabetic OLETF rats
(2). In contrast, lipid-induced
oxidative stress caused steatohepatitis and hepatic insulin resistance in mice
(3). In fact, steatosis of the
liver is an independent predictor of insulin resistance in patients with
nonalcoholic fatty liver disease
(4).It remains unclear whether hepatic steatosis causally contributes to
insulin resistance or whether it is merely a resulting pathology. Excessive
dietary free fatty acid
(FFA)2 flux into the
liver via the portal vein may cause fatty liver disease and hepatic insulin
resistance. Indeed, elevated plasma FFA concentrations correlate with obesity
and decreased target tissue insulin sensitivity
(5).Experimentally, lipid infusion or a high fat diet that increases
circulating FFA levels promotes insulin resistance in the liver. Candidate
events linking FFA to insulin resistance in vivo are the
up-regulation of SREBP-1c (6),
inflammation caused by activation of c-Jun amino-terminal kinase (JNK)
(7) or IKKβ
(8), endoplasmic reticulum (ER)
stress (9), ceramide
(10,
11), and TRB3
(12).However, which event is the direct and initial target of FFA in the liver
is unclear. Insulin resistance induced by lipid infusion or a high fat diet is
complex and may be accompanied by alterations not restricted to the liver,
making it difficult to determine the contribution of FFAs to hepatic insulin
resistance. For example, hyperinsulinemia and hyperglycemia secondary to the
initial event also may contribute to the development of diet-induced insulin
resistance in vivo
(6).To address the early event(s) triggering the development of high fat diet-
or obesity-induced insulin resistance, we investigated the molecular
mechanism(s) underlying the direct action of FFA on hepatocytes to cause
insulin resistance in vitro, using the rat hepatocyte cell line
H4IIEC3. We found that mitochondria-derived reactive oxygen species (ROS) were
a cause of palmitate-induced insulin resistance in hepatocytes. 相似文献
972.
Many research groups have sought to measure phase response curves (PRCs) from real neurons. However, methods of estimating
PRCs from noisy spike-response data have yet to be established. In this paper, we propose a Bayesian approach for estimating
PRCs. First, we analytically obtain a likelihood function of the PRC from a detailed model of the observation process formulated
as Langevin equations. Then we construct a maximum a posteriori (MAP) estimation algorithm based on the analytically obtained
likelihood function. The MAP estimation algorithm derived here is equivalent to the spherical spin model. Moreover, we analytically
calculate a marginal likelihood corresponding to the free energy of the spherical spin model, which enables us to estimate
the hyper-parameters, i.e., the intensity of the Langevin force and the smoothness of the prior.
Action Editor: John Rinzel 相似文献
973.
Keisuke Obase Joo Young Cha Jong Kyu Lee Sang Yong Lee Jin Ho Lee Kun Woo Chun 《Mycorrhiza》2009,20(1):39-49
We investigated the ectomycorrhizal (ECM) fungal colonization status of Pinus thunbergii mature trees and regenerating seedlings varying in age in coastal pine forests on the east coast of Korea. We established
one 20 × 20-m plot at each of two study sites at P. thunbergii coastal forests in Samcheok. Fifty soil blocks (5 × 5 × 15 cm) were sampled at regular intervals, and ten P. thunbergii seedlings of age 0, 1–3, 3–5, and 5–10 years were sampled in each study plot. In total of 27 ECM fungal taxa, Cenococcum geophilum was dominant, followed by Russula sp., Sebacina sp., and unidentified Cortinuris sp. in mature trees. In 0-year-old seedlings, some fungal species such as Sebacina sp., C. geophilum, and unidentified Cortinarius sp. were dominant whereas only C. geophilum was dominant after 1 year, and there were no apparent succession patterns in ECM fungal compositions beyond a host age of
1 year. Most ECM fungal taxa that had colonized seedlings of each age class were also observed in roots of mature trees in
each site. These taxa accounted for 86.7–100% and 96.4–98.4% of ECM abundance in seedlings and mature trees, respectively.
The results indicate that the species composition of ECM fungal taxa colonizing seedlings of different age in forests is similar
to that of surrounding mature trees. Our results also showed that C. geophilum is a common and dominant ECM fungus in P. thunbergii coastal forests and might play a significant role in their regeneration. 相似文献
974.
Parajuli D Adhikari CR Kawakita H Yamada S Ohto K Inoue K 《Bioresource technology》2009,100(2):1000-1002
Recovery of Au(III) from hydrochloric acid medium by using crosslinked chestnut pellicle (CCP) gel was studied. Strong selectivity was observed for Au(III) showing negligible affinity for other precious metals and some base metal ions tested. The adsorption isotherm study exhibited the maximum loading capacity of the gel as high as 10.6 mol or about 2.1 kg gold per kg dry weight of gel. The reduction of Au(III) ion to elemental form during adsorption process is expected to be the reason of high selectivity and high capacity for Au(III). Kinetic studies at various temperatures confirm an endothermic adsorption process following the pseudo-first order rate law. 相似文献
975.
Taishi Sugawara Keisuke Ito Mitsunori Shiroishi Hidetsugu Asada Tatsuro Shimamura Norimichi Nomura Keiko Abe Takuya Kobayashi 《Biochemical and biophysical research communications》2009,382(4):704-710
Human TAS2 receptors (hTAS2Rs) perceive bitter tastants, but few studies have explored the structure-function relationships of these receptors. In this paper, we report our trials on the large-scale preparations of hTAS2Rs for structural analysis. Twenty-five hTAS2Rs were expressed using a GFP-fusion yeast system in which the constructs and the culture conditions (e.g., the signal sequence, incubation time and temperature after induction) were optimized by measuring GFP fluorescence. After optimization, five hTAS2Rs (hTAS2R7, hTAS2R8, hTAS2R16, hTAS2R41, and hTAS2R48) were expressed at levels greater than 1 mg protein/L of culture, which is a preferable level for purification and crystallization. Among these five bitter taste receptors, hTAS2R41 exhibited the highest detergent solubilization efficiency of 87.1% in n-dodecyl-β-d-maltopyranoside (DDM)/cholesteryl hemisuccinate (CHS). Fluorescence size-exclusion chromatography showed that hTAS2R41 exhibited monodispersity in DDM/CHS without aggregates, suggesting that hTAS2R41 is a good target for future crystallization trials. 相似文献
976.
Kana Miyamoto Ken Ninomiya Koh-Hei Sonoda Hiroko Hoshi Ryotaro Iwasaki Hiroya Miyamoto Shigeyuki Yoshida Yuiko Sato Hideo Morioka Kazuhiro Chiba Kensuke Egashira Yoshiaki Toyama 《Biochemical and biophysical research communications》2009,383(3):373-377
Monocyte chemoattractant protein-1 (MCP-1) is a chemokine that plays a critical role in the recruitment and activation of leukocytes. Here, we describe that multinuclear osteoclast formation was significantly inhibited in cells derived from MCP-1-deficient mice. MCP-1 has been implicated in the regulation of osteoclast cell-cell fusion; however defects of multinuclear osteoclast formation in the cells from mice deficient in DC-STAMP, a seven transmembrane receptor essential for osteoclast cell-cell fusion, was not rescued by recombinant MCP-1. The lack of MCP-1 in osteoclasts resulted in a down-regulation of DC-STAMP, NFATc1, and cathepsin K, all of which were highly expressed in normal osteoclasts, suggesting that osteoclast differentiation was inhibited in MCP-1-deficient cells. MCP-1 alone did not induce osteoclastogenesis, however, the inhibition of osteoclastogenesis in MCP-1-deficient cells was restored by addition of recombinant MCP-1, indicating that osteoclastogenesis was regulated in an autocrine/paracrine manner by MCP-1 under the stimulation of RANKL in osteoclasts. 相似文献
977.
C. T. Miyamoto J. Rocha De Sant’anna C. C. Da Silva Franco M. M. Cunico O. G. Miguel L. C. Côcco C. I. Yamamoto C. CorrêaJr M. A. A. De Castro-Prado 《Folia microbiologica》2009,54(6):493-498
Eucalyptus globulus essential oil was evaluated for its genotoxic potential using a somatic segregation assay and a diploid strain of the fungus
Aspergillus nidulans, heterozygous for nutritional and conidia color markers. The main compounds of the current essential oil sample were eucalyptol
(49.0 %), α-pinene (8.9), β-pinene (1.5), globulol (6.9), α-eudesmol (1.12), spathulenol (1.42), γ-cadinene (1.45), trans-β-elemenone (1.23) and aromandendrene (2.3), totaling 74 % of oil. Oil at 0.12 and 0.25 μL/mL was found to increase the mitotic
instability of the original diploid strain and the number of diploid mitotic recombinants of A. nidulans. The genotoxicity of the oil was associated with the induction of mitotic crossing-over or with oil-broken chromosomes. 相似文献
978.
Naoki Watanabe Kentaro Hiramatsu Rieko Miyamoto Kaoru Yasuda Naoko Oshima Dai Shiba Toshio Mochizuki Shoichi Maruyama Yuko Wakamatsu Hisashi Hashimoto 《FEBS letters》2009,583(12):2108-2113
Glis3 is a member of the Gli-similar subfamily. GLIS3 mutations in humans lead to neonatal diabetes, hypothyroidism, and cystic kidney disease. We generated Glis3-deficient mice by gene-targeting. The Glis3−/− mice had significant increases in the basal blood sugar level during the first few days after birth. The high levels of blood sugar are attributed to a decrease in the Insulin mRNA level in the pancreas that is caused by impaired islet development and the subsequent impairment of Insulin-producing cell formation. The pancreatic phenotypes indicate that the Glis3-deficient mice are a model for GLIS3 mutation and diabetes mellitus in humans. 相似文献
979.
Keiichi Miyamoto Masaki Atarashi Hideki Kadozono Masakazu Shibata Yoshihiro Koyama Masanori Okai Akinobu Inakuma Eiichi Kitazono Hiroaki Kaneko Takafumi Takebayashi Takashi Horiuchi 《International journal of biological macromolecules》2009,45(1):33-41
Effective application of elastin materials for vascular grafts in tissue engineering requires these materials to retain the elastic and biological properties of native elastin. To clarify the influence of soluble elastin isotypes on vascular smooth muscle cells (VSMCs), soluble elastin was prepared from insoluble elastin by hydrolysis with oxalic acid. Its fractions were separated and classified into three isotypes. Elastin retaining 2.25 mol% of cross-linked structures exhibited significant differentiation of VSMCs, which adhered to the elastin with contraction phenotypes similar to that of native elastin, causing proliferation to cease. This trend was more strongly demonstrated in cotton-like elastin fibers with a new cross-linker. The results suggest that elastin isotypes could be applied as new effective biomaterials for suppressing intimal hyperplasia in vascular grafts. 相似文献
980.
Hisashi Hashimoto Rieko Miyamoto Naoki Watanabe Dai Shiba Kenjiro Ozato Chikako Inoue Yuko Kubo Akihiko Koga Tomoko Jindo Takanori Narita Kiyoshi Naruse Kazuko Ohishi Keiko Nogata Tadasu Shin-I Shuichi Asakawa Nobuyoshi Shimizu Tomotsune Miyamoto Toshio Mochizuki Takahiko Yokoyama Hiroshi Hori Hiroyuki Takeda Yuji Kohara Yuko Wakamatsu 《PloS one》2009,4(7)
Polycystic kidney disease (PKD) is a common hereditary disease in humans. Recent studies have shown an increasing number of ciliary genes that are involved in the pathogenesis of PKD. In this study, the Gli-similar3 (glis3) gene was identified as the causal gene of the medaka pc mutant, a model of PKD. In the pc mutant, a transposon was found to be inserted into the fourth intron of the pc/glis3 gene, causing aberrant splicing of the pc/glis3 mRNA and thus a putatively truncated protein with a defective zinc finger domain. pc/glis3 mRNA is expressed in the epithelial cells of the renal tubules and ducts of the pronephros and mesonephros, and also in the pancreas. Antisense oligonucleotide-mediated knockdown of pc/glis3 resulted in cyst formation in the pronephric tubules of medaka fry. Although three other glis family members, glis1a, glis1b and glis2, were found in the medaka genome, none were expressed in the embryonic or larval kidney. In the pc mutant, the urine flow rate in the pronephros was significantly reduced, which was considered to be a direct cause of renal cyst formation. The cilia on the surface of the renal tubular epithelium were significantly shorter in the pc mutant than in wild-type, suggesting that shortened cilia resulted in a decrease in driving force and, in turn, a reduction in urine flow rate. Most importantly, EGFP-tagged pc/glis3 protein localized in primary cilia as well as in the nucleus when expressed in mouse renal epithelial cells, indicating a strong connection between pc/glis3 and ciliary function. Unlike human patients with GLIS3 mutations, the medaka pc mutant shows none of the symptoms of a pancreatic phenotype, such as impaired insulin expression and/or diabetes, suggesting that the pc mutant may be suitable for use as a kidney-specific model for human GLIS3 patients. 相似文献