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1.
目的研究Roux-en-Y胃旁路术对2型糖尿病大鼠肾脏非对称性二甲基精氨酸(ADMA)代谢的影响。方法 40只SD大鼠,随机分为正常对照组(NC组,n=8)和糖尿病模型组(32只)。糖尿病模型组成模30只,随机分为糖尿病对照组(DC组,n=8)、糖尿病假手术组(DSO组,n=8)及糖尿病手术组(DO,n=14),DO组行胃旁路术,DSO组行胃窦十二指肠离断原位吻合。检测术前、术后1、2、4、8周血胰高血糖素样肽(GLP-1)水平,测定术前、术后8周空腹血糖(FBG),肾脏ADMA、血尿素氮(BUN)、肌酐(Cr)、一氧化氮(NO)水平,一氧化氮合酶(NOS)活性;检测蛋白质精氨酸甲基转移酶1(PRMT1)mRNA及二甲基精氨酸二甲胺水解酶1(DDAH1)mRNA,PRMT1蛋白表达水平,PAS染色观察肾脏组织学变化。结果随着手术时间延长,D0组GLP-1水平增加,其余各组无明显变化(P0.05),术后8周,DC和DSO组较DO组和NC组FBG、BUN、Cr、ADMA水平,PRMT1mRNA和蛋白表达水平均明显升高(P0.05),NO、NOS、水平、DDAH1的mRNA表达明显降低(P0.05);PAS染色示DC组和DSO组肾小球基质沉积,阳性染色物增多,余无明显变化。结论 2型糖尿病肾脏组织中的ADMA升高;胃旁路术促进ADMA代谢,改善了肾功能。 相似文献
2.
Nitric oxide plays a crucial role in cardiovascular homeostasis, with important vasodilatory, anti-thrombotic and anti-atherogenic
properties. β-Adrenergic receptors (βARs), present on a wide variety of cardiovascular cells, including vascular endothelial
cells, platelets, cardiac myocytes and leukocytes, have long been established as key players in maintaining cardiovascular
homeostatic control. During the last few years a wealth of evidence has emerged which directly links stimulation of these
cardiovascular βARs to nitric oxide (NO) generation, suggesting a new and important mechanism of adrenergic control of cardiovascular
function. This review explores the cardiovascular cell systems in which this coupling of βARs and NO occurs, the intracellular
signalling and regulatory mechanisms involved and the abnormalities in βAR-NO oxide coupling found in cardiovascular disease
states.
Received 30 September 2005; received after revision 24 November 2005; accepted 24 January 2006 相似文献
3.
J. L. Boucher C. Moali J. P. Tenu 《Cellular and molecular life sciences : CMLS》1999,55(8-9):1015-1028
Nitric oxide (NO) is a recently discovered mediator produced by mammalian cells. It plays a key role in neurotransmission,
control of blood pressure, and cellular defense mechanisms. Nitric oxide synthases (NOSs) catalyze the oxidation of L-arginine
to NO and L-citrulline. NOSs are unique enzymes in that they possess on the same polypeptidic chain a reductase domain and
an oxygenase domain closely related to cytochrome P450s. NO and superoxide formation as well as NOS stability are finely regulated
by Ca2+/calmodulin interactions, by the cofactor tetrahydrobiopterin, and by substrate availability. Strong interactions between
the L-arginine-metabolizing enzymes are clearly demonstrated by competition between NOSs and arginases for L-arginine utilization,
and by potent inhibition of arginase activity by Nω-hydroxy-L-arginine, an intermediate in the L-arginine to NO pathway. 相似文献
4.
Intraluminal injections (15 l) of either concanavalin A (125 g) or ionophore A 23187 (0.01 mol) induced a decidual cell reaction (DCR) in the uterus of day 4.5 pseudopregnant mice. However, when these agents were administered in different combinations with each other or with CaCl2 (15 mol) and phorbol-12-myristate-13-acetate (1.6 nmol), interacting effects occurred to either enhance or inhibit each of the others' independent deciduogenic capacities. The results suggest that the polyphosphatidylinositol pathway and Ca2+ are involved in the induction of the DCR in mice with complex interactions occurring between the active components of the pathway to modulate the outcome of the transformation process. 相似文献
5.
Kim DS Jeong YM Moon SI Kim SY Kwon SB Park ES Youn SW Park KC 《Cellular and molecular life sciences : CMLS》2006,63(22):2661-2668
Indole-3-carbinol (I3C) has been found to act against several types of cancer, while ultraviolet B (UVB) is known to induce
the apoptosis of human melanoma cells. Here, we investigated whether I3C can sensitize G361 human melanoma cells to UVB-induced
apoptosis. We examined the effects of combined I3C and UVB (I3C/UVB) at various dosages. I3C (200 μM)/UVB (50 mJ/cm2) synergistically reduced melanoma cell viability, whereas I3C (200 μM) or UVB (50 mJ/cm2), separately, had little effect on cell viability. DNA fragmentation assays indicated that I3C/UVB induced apoptosis. Further
results show that I3C/UVB activates caspase-8, −3, and Bid and causes the cleavage of poly(ADP-ribose) polymerase. Moreover,
I3C decreased the expression of the anti-apoptotic protein, Bcl-2, whereas UVB increased the translocation of Bax to mitochondria.
Thus, an increased Bax/Bcl-2 ratio by I3C/UVB may result in melanoma apoptosis. In conclusion, our study demonstrated that
I3C sensitizes human melanoma cells by down-regulating Bcl-2.
Received 5 July 2006; received after revision 25 August 2006; accepted 11 September 2006 相似文献
6.
The rapid migration of intestinal epithelial cells (IEC) is important for the healing of mucosal wounds. We have previously
shown that polyamine depletion inhibits migration of IEC-6 cells. Akt activation and its downstream target GSK-3β have been
implicated in the regulation of migration. Here we investigated the significance of elevated phosphatidylinositol 3-kinase
(PI3K)/Akt signaling on migration of polyamine-depleted cells. Polyamine-depleted cells had high Akt (Ser473) and GSK-3β (Ser9)
phosphorylation. Pretreatment with 20 μM LY294002 (PI3K inhibitor) for 30 min inhibited phosphorylation of Akt, increased
migration by activating Rac1 in polyamine-depleted IEC-6 cells, and restored the actin structure similar to that in cells
grown in control medium. Treatment of cells with a GSK-3β inhibitor (AR-A014418) altered the actin cytoskeleton and inhibited
migration, mimicking the effects of polyamine depletion. Thus, our results indicate that sustained activation of Akt in response
to polyamine depletion inhibits migration through GSK-3β and Rac1.
Received 25 August 2006; received after revision 3 October 2006; accepted 16 October 2006 相似文献
7.
Vanin AF Bevers LM Slama-Schwok A van Faassen EE 《Cellular and molecular life sciences : CMLS》2007,64(1):96-103
Cultured bEND.3 endothelial cells show a marked increase in NO production when subjected to anoxia, even though the normal
arginine pathway of NO formation is blocked due to absence of oxygen. The rate of anoxic NO production exceeds basal unstimulated
NO synthesis in normoxic cells. The anoxic release of NO is mediated by endothelial nitric oxide synthase (eNOS), can be abolished
by inhibitors of NOS and is accompanied by consumption of intracellular nitrite. The anoxic NO release is unaffected by the
xanthine oxidase inhibitor oxypurinol. The phenomenon is attributed to anoxic reduction of intracellular nitrite by eNOS,
and its magnitude and duration suggests that the nitrite reductase activity of eNOS is relevant for fast NO delivery in hypoxic
vascular tissues.
Received 20 August 2006; received after revision 21 September 2006; accepted 8 November 2006 相似文献
8.
Interleukin-17 stimulates inducible nitric oxide synthase-dependent toxicity in mouse beta cells 总被引:2,自引:0,他引:2
Miljkovic D Cvetkovic I Momcilovic M Maksimovic-Ivanic D Stosic-Grujicic S Trajkovic V 《Cellular and molecular life sciences : CMLS》2005,62(22):2658-2668
The influence of the proinflammatory cytokine interleukin (IL)-17 on inducible nitric oxide (NO) synthase (iNOS)-mediated
NO release was investigated in the mouse insulinoma cell line MIN6 and mouse pancreatic islets. IL-17 markedly augmented iNOS
mRNA/protein expression and subsequent NO production induced in MIN6 cells or pancreatic islets by different combinations
of interferon-γ, tumor necrosis factor-α, and IL-1β. The induction of iNOS by IL-17 was preceded by phosphorylation of p38
mitogen-activated protein kinase (MAPK), and inhibition of p38 MAPK activation completely abolished IL-17-stimulated NO release.
IL-17 enhanced the NO-dependent toxicity of proinflammatory cytokines toward MIN6 cells, while IL-17-specific neutralizing
antibody partially reduced the NO production and rescued insulinoma cells and pancreatic islets from NO-dependent damage induced
by activated T cells. Finally, a significant increase in blood IL-17 levels was observed in a multiple low-dose streptozotocin
model of diabetes, suggesting that T cell-derived IL-17 might be involved in NO-dependent damage of beta cells in this disease.
Received 14 June 2005; received after revision 17 September 2005; accepted 21 September 2005 相似文献
9.
Shafqat J Melles E Sigmundsson K Johansson BL Ekberg K Alvelius G Henriksson M Johansson J Wahren J Jörnvall H 《Cellular and molecular life sciences : CMLS》2006,63(15):1805-1811
Using surface plasmon resonance (SPR) and electrospray mass spectrometry (ESI-MS), proinsulin C-peptide was found to influence
insulin-insulin interactions. In SPR with chip-bound insulin, C-peptide mixed with analyte insulin increased the binding,
while alone C-peptide did not. A control peptide with the same residues in random sequence had little effect. In ESI-MS, C-peptide
lowered the presence of insulin hexamer. The data suggest that C-peptide promotes insulin disaggregation. Insulin/insulin
oligomer μM dissociation constants were determined. Compatible with these findings, type 1 diabetic patients receiving insulin
and C-peptide developed 66% more stimulation of glucose metabolism than when given insulin alone. A role of C-peptide in promoting
insulin disaggregation may be important physiologically during exocytosis of pancreatic β-cell secretory granulae and pharmacologically
at insulin injection sites. It is compatible with the normal co-release of C-peptide and insulin and may contribute to the
beneficial effect of C-peptide and insulin replacement in type 1 diabetics.
Received 3 May 2006; received after revision 9 June 2006; accepted 12 June 2006 Free Online Access 相似文献
10.
Tang J Wu YM Zhao P Yang XM Jiang JL Chen ZN 《Cellular and molecular life sciences : CMLS》2008,65(18):2933-2942
Mechanism of HAb18G/CD147 underlying the metastasis process of human hepatoma cells has not been determined. In the present
study, we found that integrin α3β1 colocalizes with HAb18G/CD147 in human 7721 hepatoma cells. The enhancing effect of HAb18G/CD147
on adhesion, invasion capacities and matrix metalloproteinases (MMPs) secretion was decreased by integrin α3β1 antibodies
(p<0.01). The expressions of integrin downstream molecules including focal adhesion kinase (FAK), phospho-FAK (p-FAK), paxillin,
and phospho-paxillin (p-paxillin) were increased in human hepatoma cells overexpressing HAb18G/CD147. Deletion of HAb18G/CD147
reduces the quantity of focal adhesions and rearranges cytoskeleton. Wortmannin and LY294002, specific phosphatidylinositol
kinase (PI3K) inhibitors, reversed the effect of HAb18G/CD147 on the regulation of intracellular Ca2+ mobilization, significantly reducing cell adhesion, invasion and MMPs secretion potential (p<0.01). Together, these results suggest that HAb18G/CD147 enhances the invasion and metastatic potentials of human hepatoma
cells via integrin α3β1-mediated FAK-paxillin and FAKPI3K-Ca2+ signal pathways.
Received 5 June 2008; received after revision 16 July 2008; accepted 23 July 2008 相似文献
11.
N. K. Mishra 《Cellular and molecular life sciences : CMLS》1979,35(9):1161-1163
Summary Electron microscopy of the partially heat denatured ribosomal DNA (rDNA) from sea urchin (Lytechinus variegatus) sperm has demonstrated that it consists of repeating units of 3.6±0.2 m, corresponding to a mol.wt of 7.2±0.4×106. Based on differential denaturability, each repeat unit is divided into 2 regions. The larger region of 2.47±0.11 m (mol.wt 4.9±0.22×106) corresponds in length to the ribosomal precursor RNA of sea urchins and the smaller, GC-rich, subunit of 1.16±0.09 m (mol.wt 2.3±0.18×106) is presumed to contain non-transcribed spacer sequences.Acknowledgments. This paper is dedicated to the memory of Dr D. P. Costello whose insprration made this work possible. I gratefully acknowledge the valuable advice of Drs D.W. Stafford and M.A. Bleyman. 相似文献
12.
In renal carcinoma cells (RCC4) hypoxia inducible factor-1 (HIF-1) is constitutively expressed due to a von Hippel Lindau
protein deficiency, but can be degraded by calpain, independently of the 26S proteasome, when exposed to hypoxia/nitric oxide
(NO). In this study we examined molecular mechanisms to explain calpain activation. The inability of hypoxia/NO to degrade
HIF-1α in respiratory-deficient RCC4-ρ0 cells pointed to the requirement for mitochondria-derived reactive oxygen species.
A prerequisite for O
2
−
in combination with NO to destabilize HIF-1α was corroborated in RCC4-p0 cells, when the redox cycler 2,3-dimethoxy-1,4-naphthoquinone
was used as a source of superoxide. Degradation of HIF-1α required intracellular calcium transients and calpain activation.
Using uric acid to interfere with signal transmission elicited by NO/O
2
−
blocked HIF-1α degradation and attenuated a calcium increase. We conclude that an oxidative signal as a result of NO/O
2
−
coformation triggers a calcium increase that activates calpain to degrade HIF-1α, independently of the proteasome.
Received 14 August 2007; received after revision 4 October 2007; accepted 22 October 2007 相似文献
13.
Sniekers M Foulon V Mannaerts GP Van Maldergem L Mandel H Gelb BD Casteels M Van Veldhoven PP 《Cellular and molecular life sciences : CMLS》2006,63(13):1553-1563
The identification of 2-hydroxyphytanoyl-CoA lyase (2-HPCL), a thiamine pyrophosphate (TPP)-dependent peroxisomal enzyme involved
in the α-oxidation of phytanic acid and of 2-hydroxy straight chain fatty acids, pointed towards a role of TPP in these processes.
Until then, TPP had not been implicated in mammalian peroxisomal metabolism. The effect of thiamine deficiency on 2-HPCL and
α-oxidation has not been studied, nor have possible adverse effects of deficient α-oxidation been considered in the pathogenesis
of diseases associated with thiamine shortage, such as thiamine-responsive megaloblastic anemia (TRMA). Experiments with cultured
cells and animal models showed that α-oxidation is controlled by the thiamine status of the cell/tissue/organism, and suggested
that some pathological consequences of thiamine starvation could be related to impaired α-oxidation. Whereas accumulation
of phytanic acid and/or 2-hydroxyfatty acids or their α-oxidation intermediates in TRMA patients given a normal supply of
thiamine is unlikely, this may not be true when malnourished.
Received 23 December 2005; received after revision 10 April 2006; accepted 28 April 2006 相似文献
14.
An animal unable to synthesize ascorbic acid uniquely minicks human and non-human primates. Therefore, in this study we used the rainbow trout, a teleost fish, as the model animal to study the importance of dietary ascorbic acid on the fertilizing ability of sperm. A high concentration of ascorbic acid in semen plays a key role in maintaining the genetic integrity of sperm cells, by preventing oxidative damage to sperm DNA. This study will show that the concentration of asorbic acid in seminal plasma refelcts the dietary fed either an ascorbate-free diet (from 4.74±0.9 to 0.16±0.08 g ml–1) or an ascorbate-rich diet (from 37.9±4.7 to 17.7± 3.2 g ml–1) during the sperimnation season. The relationship between ascrobate status and fertility was studied in six groups of fish fed graded levels of ascorbic acid, which sperimated over a 150-day-period. Sperm from individual males was used to fertilize several batches of eggs. When the seminal plasma ascorbate concentration decreased to 7.3 g ml–1 a significant decrease of fertilization rate and the hatching rate of embryos resulted. This is the first evidence that dietary ascorbate level directly affected sperm quality and influenced male fertility in a scruvy-prone vertebrate. 相似文献
15.
M. Takei A. Umeyama N. Shoji S. Arihara K. Endo 《Cellular and molecular life sciences : CMLS》1993,49(2):145-149
Histamine release from rat peritoneal mast cells induced by anti-IgE was essentially complete within 4–5 min. Xestobergsterol A and B, which are constituents of the Okinawan marine spongeXestospongia bergquistia Fromont, dose-dependently inhibited anti-IgE-induced histamine release from rat mast cells. The IC50 values of xestobergsterol A and B for histamine release in mast cells activated by anti-IgE were 0.07 and 0.11 M, respectively. Anti-IgE stimulated PI-PLC activity in a mast cell membrane preparation. Xestobergsterol A dose-dependently inhibited the generation of IP3 and membrane-bound PI-PLC activity. Moreover, xestobergsterol A inhibited Ca2+-mobilization from intracellular Ca2+-stores as well as histamine release in mast cells activated by anti-IgE. On the other hand, xestobergsterol B did not inhibit the membrane-bound and cytosolic PI-PLC activity, IP3 generation or the initial rise in [Ca2+]i in mast cells activated by anti-IgE. These results suggest that the mechanism of inhibition by xestobergsterol A of the initial rise in [Ca2+]i, of the generation of IP3, and of histamine release induced by anti-IgE, was through the inhibition of PI-PLC activity. 相似文献
16.
Endothelium-derived nitric oxide and vascular physiology and pathology 总被引:13,自引:0,他引:13
J.-F. Arnal A.-T. Dinh-Xuan M. Pueyo B. Darblade J. Rami 《Cellular and molecular life sciences : CMLS》1999,55(8-9):1078-1087
In 1980, Furchgott and Zawadzki demonstrated that the relaxation of vascular smooth muscle cells in response to acetylcholine
is dependent on the anatomical integrity of the endothelium. Endothelium-derived relaxing factor was identified 7 years later
as the free radical gas nitric oxide (NO). In endothelium, the amino acid L-arginine is converted to L-citrulline and NO by
one of the three NO synthases, the endothelial isoform (eNOS). Shear stress and cell proliferation appear to be, quantitatively,
the two major regulatory factors of eNOS gene expression. However, eNOS seems to be mainly regulated by modulation of its
activity. Stimulation of specific receptors to various agonists (e.g., bradykinin, serotonin, adenosine, ADP/ATP, histamine,
thrombin) increases eNOS enzymatic activity at least in part through an increase in intracellular free Ca2+. However, the mechanical stimulus shear stress appears again to be the major stimulus of eNOS activity, although the precise
mechanisms activating the enzyme remain to be elucidated. Phosphorylation and subcellular translocation (from plasmalemmal
caveolae to the cytoskeleton or cytosol) are probably involved in these regulations. Although eNOS plays a major vasodilatory
role in the control of vasomotion, it has not so far been demonstrated that a defect in endothelial NO production could be
responsible for high blood pressure in humans. In contrast, a defect in endothelium-dependent vasodilation is known to be
promoted by several risk factors (e.g., smoking, diabetes, hypercholesterolemia) and is also the consequence of atheroma (fatty
streak infiltration of the neointima). Several mechanisms probably contribute to this decrease in NO bioavailability. Finally,
a defect in NO generation contributes to the pathophysiology of pulmonary hypertension. Elucidation of the mechanisms of eNOS
enzyme activity and NO bioavailability will contribute to our understanding the physiology of vasomotion and the pathophysiology
of endothelial dysfunction, and could provide insights for new therapies, particularly in hypertension and atherosclerosis. 相似文献
17.
Arterial thrombosis is the single most common cause of death and disability in industrialized societies and is the primary
pathogenic mechanism underlying acute myocardial infarction and ischemic stroke. Platelets play a central role in this process,
and as a consequence, a great deal of effort has gone into identifying the mechanisms regulating the adhesive function of
platelets. Platelet adhesion is controlled by intracellular signaling pathways, with growing evidence for a major role for
phosphoinositide 3-kinases (PI3Ks) in this process. Platelets express all type I PI3K isoforms, including p110α, p110β, p110δ
and p110γ, with recent evidence suggesting important roles for p110γ and p110β in regulating distinct phases of the platelet
activation process. Deficiency of p110 γ or inhibition of p110β produces a marked defect in arterial thrombosis without a
corresponding increase in bleeding time, raising the possibility that inhibition of one or more PI3K isoforms may represent
an effective antithrombotic approach.
Received 3 January 2006; received after revision 20 February 2006; accepted 20 February 2006 相似文献
18.
Hellgren M Strömberg P Gallego O Martras S Farrés J Persson B Parés X Höög JO 《Cellular and molecular life sciences : CMLS》2007,64(4):498-505
The metabolism of all-trans- and 9-cis-retinol/ retinaldehyde has been investigated with focus on the activities of human, mouse and rat alcohol dehydrogenase 2
(ADH2), an intriguing enzyme with apparently different functions in human and rodents. Kinetic constants were determined with
an HPLC method and a structural approach was implemented by in silico substrate dockings. For human ADH2, the determined Km values ranged from 0.05 to 0.3 μM and kcat values from 2.3 to 17.6 min−1, while the catalytic efficiency for 9-cis-retinol showed the highest value for any substrate. In contrast, poor activities
were detected for the rodent enzymes. A mouse ADH2 mutant (ADH2Pro47His) was studied that resembles the human ADH2 setup.
This mutation increased the retinoid activity up to 100-fold. The Km values of human ADH2 are the lowest among all known human retinol dehydrogenases, which clearly support a role in hepatic
retinol oxidation at physiological concentrations.
Received 12 October 2006; received after revision 6 December 2006; accepted 8 January 2007 相似文献
19.
Summary Hexoprenaline potentiated the14C-aminopyrine uptake (a reliable index of H+ generation) of isolated rat gastric cells stimulated by 10–6–10–4 mol/l carbachol, and inhibited that in response to 10–4 mol/l histamine without and in the presence of propranolol. It is concluded that hexoprenaline acts as a partial agonist on parietal cell H2-receptors and that -adrenoceptor activation may functionally modualte gastric acid secretion.Acknowledgments. S. Maliski, Institute of Rheumatology, Warszawa, held a fellowship of the Alexander v. Humboldt-Foundation. The study was supported by the Deutsche Forschungsgemeinschaft. The skilful technical assistance of Mrs R. Maier and Mr R. Beer is gratefully acknowledged. 相似文献
20.
We report that histones H2A and H2B possess gonadotrophin-releasing activity in vitro and assess the signal transduction
pathways involved in these effects. Perifused and incubated rat anterior pituitary (AP) cells were used, and luteinizing hormone
(LH) and follicle stimulating hormone (FSH) were measured by RIA. Perifusion of cells with histone H2A (30 μM) or histone
H2B (30 μM), markedly stimulated LH release but failed to elicit any FSH response. Cells incubated with 6 or 30 μM histone
H2A showed a dose- and time-dependent stimulatory effect on both LH and FSH release which was blocked by 1 μM peptide MB35,
an 86–120 amino acid fragment of histone H2A. Incubation of pituitary cells with gonadotrophin-releasing hormone (GnRH) and
histones H2A or H2B showed a stimulatory effect on LH and FSH release which was similar to the sum of the separate effects.
Trifluoperazine, as well as ethylene glycol bis(b-aminoethyl ether) N,N,N′,N′-tetraacetic acid (EGTA), alone or in the presence
of the calcium ionophore A23187, significantly reduced the response of AP cells to histones. Various cyclic adenosine monophosphate
(cAMP) enhancers had no effect on histone-stimulated release of gonadotrophins in incubated AP cells. Our results confirm
previous evidence that histones may act as hypophysiotrophic signals. Calcium- and diacylglycerol-associated pathways, but
not cAMP, appear to participate in these effects.
Received 11 August 1997; received after revision 20 January 1998; accepted 26 January 1998 相似文献