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991.
Role for thromboxane A2 from glomerular thrombi in nephropathy with type 2 diabetic rats 总被引:6,自引:0,他引:6
Okumura M Imanishi M Okamura M Hosoi M Okada N Konishi Y Morikawa T Miura K Nakatani T Fujii S 《Life sciences》2003,72(24):2695-2705
We used rats (the Otsuka Long-Evans Tokushima Fatty strain) as a model of type 2 diabetes to find whether thromboxane (TX) A2 is involved in diabetic nephropathy, and if so, to identify where it is synthesized. We measured urinary excretion of TXB2 and 2,3-dinor-TXB2 in rats up to 60 weeks of age as markers of renal and platelet synthesis of TXA2, respectively. Some diabetic rats were given daily oral doses of OKY-046 (100 mg/kg), a TXA2 synthase inhibitor, starting when they were 10 weeks of age. Healthy Long-Evans Tokushima Otsuka rats served as the controls. Urinary excretion of protein was greater in diabetic rats at 26 weeks than in controls, and the difference increased with age. Urinary excretion of TXB2 by diabetic rats was about 150% that of controls at 14 weeks, and remained at that level. In diabetic rats, urinary excretion of 2,3-dinor-TXB2 increased with age in parallel to increases in proteinuria, but in controls, excretion of these metabolites did not change with age. In diabetic rats, OKY-046 prevented the increase in urinary excretion of both metabolites, and decreased the proteinuria. Histologic examination at 60 weeks showed intraglomerular thrombi in diabetic rats but not in controls. OKY-046 reduced intraglomerular thrombi formation and the score for glomerulosclerosis. When platelet aggregation began, more TXA2 than before was released from the thrombi that formed, and the TXA2 contributed to the progress of nephropathy in this rat model of type 2 diabetes. 相似文献
992.
HLF/HIF-2alpha is a key factor in retinopathy of prematurity in association with erythropoietin 总被引:15,自引:0,他引:15
Morita M Ohneda O Yamashita T Takahashi S Suzuki N Nakajima O Kawauchi S Ema M Shibahara S Udono T Tomita K Tamai M Sogawa K Yamamoto M Fujii-Kuriyama Y 《The EMBO journal》2003,22(5):1134-1146
An HLF (HIF-1alpha-like factor)/HIF-2alpha-knockout mouse is embryonic lethal, preventing investigation of HLF function in adult mice. To investigate the role of HLF in adult pathological angiogenesis, we generated HLF-knockdown (HLF(kd/kd)) mice by inserting a neomycin gene sandwiched between two loxP sequences into exon 1 of the HLF gene. HLF(kd/kd) mice expressing 80-20% reduction, depending on the tissue, in wild-type HLF mRNA were fertile and apparently normal. Hyperoxia-normoxia treatment, used as a murine model of retinopathy of prematurity (ROP), induced neovascularization in wild-type mice, but not in HLF(kd/kd) mice, whereas prolonged normoxia following hyperoxic treatment caused degeneration of retinal neural layers in HLF(kd/kd) mice due to poor vascularization. Cre-mediated removal of the inserted gene recovered normal HLF expression and retinal neovascularization in HLF(kd/kd) mice. Expression levels of various angiogenic factors revealed that only erythropoietin (Epo) gene expression was significantly affected, in parallel with HLF expression. Together with the results from intraperitoneal injection of Epo into HLF(kd/kd) mouse, this suggests that Epo is one of the target genes of HLF responsible for experimental ROP. 相似文献
993.
Du J Cai S Suzuki H Akhand AA Ma X Takagi Y Miyata T Nakashima I Nagase F 《Journal of cellular biochemistry》2003,88(6):1235-1246
The abnormal accumulation of methylglyoxal (MG), a physiological glucose metabolite, is strongly related to the development of diabetic complications by affecting the metabolism and functions of organs and tissues. These disturbances could modify the cell response to hormones and growth factors, including insulin-like growth factor-1 (IGF-I). In this study, we investigated the effect of MG on IGF-I-induced cell proliferation and the mechanism of the effect in two cell lines, a human embryonic kidney cell line (HEK293), and a mouse fibroblast cell line (NIH3T3). MG rendered these cells resistant to the mitogenic action of IGF-I, and this was associated with stronger and prolonged activation of ERK and over-expression of P21(Waf1/Cip1). The synergistic effect of MG with IGF-I in activation of ERK was completely abolished by PD98059 but not by a specific PI3K inhibitor, LY294002, or a specific PKC inhibitor, bisindolylmaleimide. Blocking of Raf-1 activity by expression of a dominant negative form of Raf-1 did not reduce the enhancing effect of MG on IGF-I-induced activation of ERK. However, transfection of a catalytically inactive form of MEKK1 resulted in inactivation of the MG-induced activation of ERK and partial inhibition of the enhanced activation of ERK and over-expression of p21(Waf1/Cip1) induced by co-stimulation of MG and IGF-I. These results suggested that the alteration of intracellular milieu induced by MG through a MEKK1-mediated and PI3K/PKC/Raf-1-independent pathway resulted in the modification of cell response to IGF-I for p21(Waf1/Cip1)-mediated growth arrest, which may be one of the crucial mechanisms for MG to promote the development of chronic clinical complications in diabetes. 相似文献
994.
We examined the effects of serum deprivation on myofibrillar proteolysis in chick myotubes. Myotubes were incubated with serum-free medium for 24 hours. N(tau)-methylhistidine release, as an index of myofibrillar proteolysis, as well as protease activities such as calpain, proteasome, and cathepsins (B+L and D) activities were increased by serum deprivation. These results indicate that serum deprivation induces calpain, proteasome, and cathepsins activities, resulting in an increase in myofibrillar proteolysis in chick myotubes. 相似文献
995.
Proliferating cells in the male rat anterior pituitary at 1, 3, 5, and 8 weeks of age were labeled with bromodeoxyuridine (BrdU) and studied by light and electron microscopic immunocytochemistry using anti-BrdU. They decreased in number from 402±31/mm2 at 1 week to 50±1.5/mm2 at 8 weeks, while their cell area increased by about twofold during this period. They had a slightly higher nucleus/whole cell (N/C) ratio than non-proliferating cells. According to their ultrastructure we classified them into granular and agranular cells. The percentage of granular cells ranged from 73% to 82% of all the proliferating cells during the period studied. They had many granules of various sizes and shapes, and some contained growth hormone and prolactin. Agranular cells, constituting 18–27% of proliferating cells, were small and had a high N/C ratio, indicating their immaturity. Moreover, they showed several features of folliculo-stellate (FS) cells: they showed no secretory granules in the cytoplasm, extended thin cytoplasmic processes, and sometimes they constructed a follicle among them. These results suggest: (1) the majority of proliferating cells were mature cells producing anterior pituitary hormone(s) and (2) most of the agranular proliferating cells maybe FS cells. The possibility of the latter is discussed. 相似文献
996.
Hirota A Inaba M Chen YC Abe N Taki S Yano M Kawaii S 《Bioscience, biotechnology, and biochemistry》2004,68(6):1372-1374
We isolated from soybean miso 8-hydroxyglycitein and 6-hydroxydaidzein as DPPH-radical scavengers, and elucidated their chemical structures by mass spectrometric, and (1)H- and (13)C-NMR spectrosopic analyses. These compounds showed DPPH-radical scavenging activity as high as that of alpha-tocopherol, 8-hydroxygenistein and 8-hydroxydaidzein. This is the first report of the isolation of 8-hydroxyglycitein from a natural source. 相似文献
997.
Kumazawa S Kajiya K Naito A Saito H Tuzi S Tanio M Suzuki M Nanjo F Suzuki E Nakayama T 《Bioscience, biotechnology, and biochemistry》2004,68(8):1743-1747
The interaction of a tea catechin, epigallocatechin gallate (EGCg), with the model membrane of dimyristoylphosphatidylcholine (DMPC) was studied by solid-state (31)P and (2)H NMR. The (31)P chemical shift anisotropy of the DMPC phosphate group decreased on addition of EGCg. The (2)H NMR spectrum of [4-(2)H]EGCg, which is deuterated at the 4-position, in the DMPC liposomes gave deuterium nuclei with much smaller quadrupole splittings than those in the solid phase. These (31)P and (2)H NMR observations provide direct experimental evidence that the EGCg molecule interacts with the lipid bilayers. 相似文献
998.
Nanjo Y Asatsuma S Itoh K Hori H Mitsui T 《Bioscience, biotechnology, and biochemistry》2004,68(1):112-118
We isolated and identified 10 alpha-amylase isoforms by using beta-cyclodextrin Sepharose affinity column chromatography and two-dimensional polyacrylamide gel electrophoresis from germinating rice (Oryza sativa L.) seeds. Immunoblots with anti-alpha-amylase I-1 and II-4 antibodies indicated that 8 isoforms in 10 are distinguishable from alpha-amylase I-1 and II-4. Peptide mass fingerprinting analysis showed that there exist novel isoforms encoded by RAmy3B and RAmy3C genes. The optimum temperature for enzyme reaction of the RAmy3B and RAmy3C coding isoforms resembled that of alpha-amylase isoform II-4 (RAmy3D). Furthermore, complex protein polymorphism resulted from a single alpha-amylase gene was found to occur not only in RAmy3D, but also in RAmy3B. 相似文献
999.
1000.
Yamashita D Kohzuki H Kitagawa Y Nakashima T Kikuta A Takaki M 《American journal of physiology. Heart and circulatory physiology》2004,287(1):H54-H62
Left ventricular (LV) myocardial slices were isolated from murine hearts (300 microm thick) and were stimulated at 1 Hz without external load. Mean myocardial slice O(2) consumption (MVo(2)) per minute (mMVo(2)) without stimulation was 0.97 +/- 0.14 ml O(2).min(-1).100 g LV(-1) and mean mMVo(2) with stimulation increased to 1.80 +/- 0.17 ml O(2).min(-1).100 g LV(-1) in normal Tyrode solution. Mean DeltamVo(2) (the mMVo(2) with stimulation - the mMVo(2) without stimulation) was 0.83 +/- 0.12 ml O(2).min(-1).100 g LV(-1). There were no differences between mean mMVo(2) with and without stimulation in Ca(2+)-free solution. The increases in extracellular Ca(2+) concentrations up to 14.4 mM did not affect the mMVo(2) without stimulation but significantly increased the mMVo(2) with stimulation up to 140% of control. The DeltamMVo(2) significantly increased up to 190% of the control in a dose-dependent manner. In contrast, the shortening did not increase in a dose-dependent manner. Cyclopiazonic acid (CPA; 30 microM) significantly reduced the DeltamMVo(2) to 0.27 +/- 0.06 ml O(2).min(-1).100 g LV(-1) (35% of control). The combination of 5 mM 2,3-butanedione monoxime (BDM) and 30 microM CPA did not further decrease DeltamMVo(2). Although BDM (3-5 mM) decreased the DeltamMVo(2) by 28-30% of control in a dose-independent manner, 3-5 mM BDM decreased shortening in a dose-dependent manner. Our results indicate that the DeltamMVo(2) of mouse LV slices during shortening under mechanically unloaded conditions consists of energy expenditure for total Ca(2+) handling during excitation-contraction coupling, basal metabolism, but no residual cross-bridge cycling. 相似文献