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1.
Significance and molecular targets of protein kinase A during cAMP-mediated protection of cold stored liver grafts 总被引:6,自引:0,他引:6
The use of marginal donor livers is followed by a higher frequency of primary dys- or nonfunction after transplantation.
The present study was designed to test the hypothesis that stimulation of the cAMP second-messenger signal pathway might protect
the liver from ischemic injury, laying emphasis on the role of protein kinase A-mediated signal transduction.?Rat livers were
harvested after 45 min of cardiac arrest and preserved in HTK solution for 24 h. Hepatic integrity was assessed thereafter
using a blood-free reperfusion model.?Supplementation of the preservation solution with dibutyryl-cAMP (db-cAMP) promoted
phosphorylation of BAD at Ser 112 and concomitantly mitigated mitochondrial release of cytochrome c into the cytosol. Apoptotic
cell transformation was evident in reperfused livers by positive TUNEL-staining of sinusoidal lining cells and the detection
of cleaved poly(ADP-ribose) polymerase (PARP) in tissue homogenates by western analysis. Treatment with db-cAMP was effective
in minimizing both TUNEL staining and PARP cleavage and significantly reduced postischemic enzyme leakage of alanine aminotransferase
to one half, while hepatic bile production was enhanced by approximately 60% when compared to untreated livers. This functional
improvement was accompanied by a net amelioration of portal vascular conductivity. Inhibition of A kinase-anchoring protein
with HT31 completely reversed any of the observed effects obtained by db-cAMP.?We conclude that enhancement of cellular cAMP
signal maintains hepatic integrity during and after ischemic preservation which may be attributed to protein kinase A dependent
phosphorylation of BAD in line with subsequent inhibition of mitochondria-initiated apoptosis of sinusoidal lining cells.
Received 12 July 2001; received after revision 14 August 2001; accepted 14 August 2001 相似文献
2.
目的探讨枸杞多糖(LBP)对体外培养的人肺腺癌细胞 A549的增殖抑制作用及其可能的作用机制.方法用不同浓度的LBP处理 A549细胞,MTT法检测24、48、72h时间点 LBP对 A549细胞的生长抑制率,实验设为对照组和实验组(1/2IC50作用48小时),MTT法绘制生长曲线、细胞计数计算倍增时间、流式细胞仪检测凋亡率及其细胞周期、RT PCR检测 SurvivinmRNA的变化、Westernblot检测 CyclinB1蛋白的变化,transwell体外侵袭实验观察药物对细胞体外侵袭的影响.结果 MTT显示不同浓度的LBP均能明显抑制 A549细胞的增殖且成剂量 效应关系,实验组细胞的倍增时间、凋亡率与对照组相比,均有统计学意义(P<0.05);LBP使细胞阻滞在 G2期,SurvivinmRNA表达和 CyclinB1蛋白的表达均降低,与对照组相比差异有显著性(P<0.05).结论 LBP可抑制 A549细胞的增殖,其机理可能与 LBP使 SurvivinmRNA表达下降引起细胞凋亡及 CyclinB1蛋白的表达降低造成细胞周期阻滞及抑制细胞的侵袭能力有关 相似文献
3.
Hrzenjak A Reicher H Wintersperger A Steinecker-Frohnwieser B Sedlmayr P Schmidt H Nakamura T Malle E Sattler W 《Cellular and molecular life sciences : CMLS》2004,61(12):1520-1531
-Tocopheryl-succinate (TS) is a synthetic, anti-neoplastic derivative of -tocopherol. Here we studied the effects of free and high-density lipoprotein subclass 3 (HDL3)-associated TS on the growth of human (A549) and mouse Lewis (LL2) lung carcinoma cells. Both free and HDL3-associated TS inhibited A549 growth in a time- and concentration-dependent manner. Treatment of A549 cells with TS-enriched HDL3 led to DNA fragmentation and a time-dependent decrease in immunoreactivity of poly(ADP-ribose)polymerase. Uptake experiments revealed a high capacity for selective TS uptake in excess of holoparticle endocytosis. Overexpression of scavenger receptor class B, type I (SR-BI), the prime receptor mediating selective lipid uptake, in A549 cells resulted in significantly increased selective TS uptake, a finding associated with complete cellular growth arrest. The present in vitro findings were verified in an in vivo model: tumor inoculation in C57BL6 was performed with either wild-type, -galactosidase- or SR-BI-overexpressing LL2 cells. After tumor inoculation, the animals received six consecutive intravenous injections of TS. This experimental setup resulted in significantly reduced tumor burden in animals that were inoculated with SR-BI-overexpressing LL2 cells but not in animals inoculated with wild-type or -galactocidase-transfected cells. Based on our in vitro and in vivo findings, we propose that SR-BI could provide a novel route for HDL3-mediated drug delivery of anti-neoplastic drugs.Received 8 March 2004; received after revision 7 April 2004; accepted 26 April 2004 相似文献
4.
Chronic gestational exposure to ethanol impairs insulin-stimulated survival and mitochondrial function in cerebellar neurons 总被引:6,自引:1,他引:5
Chronic gestational exposure to ethanol has profound adverse effects on brain development. In this regard, studies using
in vitro models of ethanol exposure demonstrated impaired insulin signaling mechanisms associated with increased apoptosis
and reduced mitochondrial function in neuronal cells. To determine the relevance of these findings to fetal alcohol syndrome,
we examined mechanisms of insulin-stimulated neuronal survival and mitochondrial function using a rat model of chronic gestational
exposure to ethanol. In ethanol-exposed pups, the cerebellar hemispheres were hypoplastic and exhibited increased apoptosis.
Isolated cerebellar neurons were cultured to selectively evaluate insulin responsiveness. Gestational exposure to ethanol
inhibited insulin-stimulated neuronal viability, mitochondrial function, Calcein AM retention (membrane integrity), and GAPDH
expression, and increased dihydrorosamine fluorescence (oxidative stress) and pro-apoptosis gene expression (p53, Fas-receptor,
and Fas-ligand). In addition, neuronal cultures generated from ethanol-exposed pups had reduced levels of insulin-stimulated
Akt, GSK-3β, and BAD phosphorylation, and increased levels of non-phosphorylated (activated) GSK-3β and BAD protein expression.
The aggregate results suggest that insulin-stimulated central nervous system neuronal survival mechanisms are significantly
impaired by chronic gestational exposure to ethanol, and that the abnormalities in insulin signaling mechanisms persist in
the early postnatal period, which is critical for brain development.
Received 21 January 2002; received after revision 28 February 2002; accepted 25 March 2002 相似文献
5.
K. von Schwarzenberg S. A. E. Held A. Schaub K. M. Brauer A. Bringmann P. Brossart 《Cellular and molecular life sciences : CMLS》2009,66(7):1295-1308
In order to analyze the effects of peroxisome proliferator-activated receptor-γ (PPARγ) activation on renal cell carcinomas
we utilized several cell lines that were treated with the high affinity PPARγ agonist, troglitazone. Incubation of RCC cells
with troglitazone resulted in reduced secretion of growth factors that was due to the inhibition of MAP kinase signaling and
reduced nuclear localized expression of relB and HIF1alpha. Interestingly, the cell lines used showed a different sensitivity
towards apoptosis induction that did not correlate with the inhibition of growth factors or expression of pro- and antiapoptotic
molecules. To overcome this resistance the cells were treated with a combination of troglitazone and the proteasome inhibitor,
bortezomib. The combination of both compounds induced apoptosis even in cells resistant to both agents alone, due to increased
induction of ER-stress and caspase-3 mediated cell death.
Received 03 September 2009; received after revision 02 February 2009; accepted 10 February 2009 相似文献
6.
Bernd Kaina Geoffrey P. Margison Markus Christmann 《Cellular and molecular life sciences : CMLS》2010,67(21):3663-3681
O
6-methylguanine-DNA methyltransferase (MGMT) repairs the cancer chemotherapy-relevant DNA adducts, O
6-methylguanine and O
6-chloroethylguanine, induced by methylating and chloroethylating anticancer drugs, respectively. These adducts are cytotoxic,
and given the overwhelming evidence that MGMT is a key factor in resistance, strategies for inactivating MGMT have been pursued.
A number of drugs have been shown to inactivate MGMT in cells, human tumour models and cancer patients, and O
6-benzylguanine and O
6-[4-bromothenyl]guanine have been used in clinical trials. While these agents show no side effects per se, they also inactivate
MGMT in normal tissues and hence exacerbate the toxic side effects of the alkylating drugs, requiring dose reduction. This
might explain why, in any of the reported trials, the outcome has not been improved by their inclusion. It is, however, anticipated
that, with the availability of tumour targeting strategies and hematopoetic stem cell protection, MGMT inactivators hold promise
for enhancing the effectiveness of alkylating agent chemotherapy. 相似文献
7.
目的研究青蒿水提液对肺癌A549细胞株增殖的影响和诱导凋亡的情况。方法不同浓度青蒿水提液作用于细胞不同时间,四甲基氮噻唑蓝(MTT)法检测吸光度值(A490nm)并计算增殖抑制率;AnnexinV-FITC/PI荧光染色后流式细胞仪检测细胞凋亡率;并以荧光显微镜观察细胞形态改变情况;蛋白质印迹法分析细胞凋亡相关蛋白Bax、Bcl-2的表这。结果青蒿水提液呈时间和剂量依赖性抑制A549细胞增殖;荧光显微镜下A549细胞出现不同时期凋亡特征性改变;流式细胞仪检测细胞凋亡率随着药物浓度增加而升高;A549细胞株的Bax蛋白表达量增多、Bcl-2蛋白表达量下降。结论青蒿水提液促进体外培养的A549细胞株增殖抑制并诱导凋亡,其机制可能与A549细胞Bax表达上调和Bcl-2表达下调有关。 相似文献
8.
目的 观察基膜聚糖(Lumican)基因过度表达对人肺腺癌细胞株A549体外增殖和侵袭的影响.方法 以携带人Lumican基因的重组慢病毒感染A549细胞,用嘌呤霉素(puromycin)筛选法建立稳定细胞株.分别用Real-time PCR和Western blotting方法检测A549细胞组、空载体组及Lumican感染组目的基因mRNA和蛋白的表达.运用MTT法研究Lumican基因对A549细胞增殖的影响.运用Transwell法检测Lumican基因对A549细胞侵袭的影响.结果 ①各组Lumican mRNA表达差异显著(x2=21.60,P<0.01),Lumican感染组明显高于其它两组(F=102.86,P<0.000 1),Lumican感染组的蛋白表达水平高于其它两组.②Lumican感染组在不同时间(1、2、3、4、5 d)OD(吸光度)值与A549细胞组和空载体组差异不显著(P>0.05).③各组穿膜细胞数差异显著(x2=23.49,P<0.01),Lumican感染组明显高于其它两组(F=73.92,P<0.001).结论 成功构建了Lumican高表达的人肺腺癌A549稳定细胞株,Lumican基因对人肺腺癌细胞的体外增殖能力无影响,但能增强人肺腺癌细胞的体外侵袭能力. 相似文献
9.
Chiara Riganti Iris C. Salaroglio Martha L. Pinzòn-Daza Valentina Caldera Ivana Campia Joanna Kopecka Marta Mellai Laura Annovazzi Pierre-Olivier Couraud Amalia Bosia Dario Ghigo Davide Schiffer 《Cellular and molecular life sciences : CMLS》2014,71(3):499-516
Low delivery of many anticancer drugs across the blood–brain barrier (BBB) is a limitation to the success of chemotherapy in glioblastoma. This is because of the high levels of ATP-binding cassette transporters like P-glycoprotein (Pgp/ABCB1), which effluxes drugs back to the bloodstream. Temozolomide is one of the few agents able to cross the BBB; its effects on BBB cells permeability and Pgp activity are not known. We found that temozolomide, at therapeutic concentration, increased the transport of Pgp substrates across human brain microvascular endothelial cells and decreased the expression of Pgp. By methylating the promoter of Wnt3 gene, temozolomide lowers the endogenous synthesis of Wnt3 in BBB cells, disrupts the Wnt3/glycogen synthase kinase 3/β-catenin signaling, and reduces the binding of β-catenin on the promoter of mdr1 gene, which encodes for Pgp. In co-culture models of BBB cells and human glioblastoma cells, pre-treatment with temozolomide increases the delivery, cytotoxicity, and antiproliferative effects of doxorubicin, vinblastine, and topotecan, three substrates of Pgp that are usually poorly delivered across BBB. Our work suggests that temozolomide increases the BBB permeability of drugs that are normally effluxed by Pgp back to the bloodstream. These findings may pave the way to new combinatorial chemotherapy schemes in glioblastoma. 相似文献
10.
Diana Rita Szabó Kornélia Baghy Peter M. Szabó Adrienn Zsippai István Marczell Zoltán Nagy Vivien Varga Katalin Éder Sára Tóth Edit I. Buzás András Falus Ilona Kovalszky Attila Patócs Károly Rácz Peter Igaz 《Cellular and molecular life sciences : CMLS》2014,71(5):917-932
The currently available medical treatment options of adrenocortical cancer (ACC) are limited. In our previous meta-analysis of adrenocortical tumor genomics data, ACC was associated with reduced retinoic acid production and retinoid X receptor-mediated signaling. Our objective has been to study the potential antitumoral effects of 9-cis retinoic acid (9-cisRA) on the ACC cell line NCI-H295R and in a xenograft model. Cell proliferation, hormone secretion, and gene expression have been studied in the NCI-H295R cell line. A complex bioinformatics approach involving pathway and network analysis has been performed. Selected genes have been validated by real-time qRT-PCR. Athymic nude mice xenografted with NCI-H295R have been used in a pilot in vivo xenograft model. 9-cisRA significantly decreased cell viability and steroid hormone secretion in a concentration- and time-dependent manner in the NCI-H295R cell line. Four major molecular pathways have been identified by the analysis of gene expression data. Ten genes have been successfully validated involved in: (1) steroid hormone secretion (HSD3B1, HSD3B2), (2) retinoic acid signaling (ABCA1, ABCG1, HMGCR), (3) cell-cycle damage (GADD45A, CCNE2, UHRF1), and the (4) immune response (MAP2K6, IL1R2). 9-cisRA appears to directly regulate the cell cycle by network analysis. 9-cisRA also reduced tumor growth in the in vivo xenograft model. In conclusion, 9-cisRA might represent a promising new candidate in the treatment of hormone-secreting adrenal tumors and adrenocortical cancer. 相似文献
11.
Andrey V. Kulikov Alexander S. Vdovin Boris Zhivotovsky Vladimir Gogvadze 《Cellular and molecular life sciences : CMLS》2014,71(12):2325-2333
Rapidly proliferating tumor cells easily become hypoxic. This results in acquired stability towards treatment with anticancer drugs. Here, we show that cells grown at 0.1 % oxygen are more resistant towards treatment with the conventionally used anticancer drugs doxorubicin and cisplatin. The stimulation of apoptosis, as assessed by the number of cells in the SubG1 fraction of the cell cycle, release of cytochrome c into the cytosol, activation of caspase-3, and cleavage of PARP, was markedly suppressed under low oxygen content or when hypoxia was mimicked by deferoxamine. Hypoxia or deferoxamine treatment was accompanied by stabilization of the hypoxia-inducible factor (HIF-1). The downregulation of HIF-1 using siRNA technique restored cell sensitivity to treatment under hypoxic conditions to the levels detected under normoxic conditions. In contrast to cisplatin or doxorubicin, α-tocopheryl succinate (α-TOS), a compound that targets mitochondria, stimulated cell death irrespective of the oxygen concentration. Moreover, under hypoxic condition cell death induced by α-TOS was even enhanced. Thus, α-TOS can successfully overcome resistance to treatment caused by hypoxia, which makes α-TOS an attractive candidate for antitumor therapy via mitochondrial targeting. 相似文献
12.
Jessica L. Slack Corey P. Causey Paul R. Thompson 《Cellular and molecular life sciences : CMLS》2011,68(4):709-720
The recent approvals of anticancer therapeutic agents targeting the histone deacetylases and DNA methyltransferases have highlighted
the important role that epigenetics plays in human diseases, and suggested that the factors controlling gene expression are
novel drug targets. Protein arginine deiminase 4 (PAD4) is one such target because its effects on gene expression parallel
those observed for the histone deacetylases. We demonstrated that F- and Cl-amidine, two potent PAD4 inhibitors, display micromolar
cytotoxic effects towards several cancerous cell lines (HL-60, MCF7 and HT-29); no effect was observed in noncancerous lines
(NIH 3T3 and HL-60 granulocytes). These compounds also induced the differentiation of HL-60 and HT29 cells. Finally, these
compounds synergistically potentiated the cell killing effects of doxorubicin. Taken together, these findings suggest PAD4
inhibition as a novel epigenetic approach for the treatment of cancer, and suggest that F- and Cl-amidine are candidate therapeutic
agents for this disease. 相似文献
13.
Sanchez-Perez I Rodriguez-Hernandez CJ Manguan-García C Torres A Perona R Murguía JR 《Cellular and molecular life sciences : CMLS》2004,61(6):700-708
The immunosuppressants tacrolimus (FK506) and cyclosporin A (CsA) have increased the survival rates in organ transplantation. Both drugs inhibit the protein phosphatase calcineurin (CaN) in activated T cells, exhibiting similar side-effects. Diabetes is observed more often in FK506 than CsA therapy, probably due to inhibition of new molecular targets other than CaN. We studied FK506 toxicity in mammalian cells. FK506, but not CsA, regulated p38 activation by osmotic stress, and decreased viability in osmostressed cells. In addition, FK506 treatment strongly increased the phosphorylation of the eukaryotic initiation factor-2a (eIF-2a) subunit. eIF-2a phosphorylation, p38 inhibition and cell lethality were relieved by addition of excess amino acids to the medium, suggesting that amino acid availability mediated FK506 toxicity. Therefore, these FK506-dependent responses could be relevant to the non-therapeutic effects of FK506 therapy.Received 16 October 2003; received after revision 8 January 2004; accepted 14 January 2004 相似文献
14.
Angela Dittmer Kristina Hohlfeld Jana Lützkendorf Lutz P. Müller Jürgen Dittmer 《Cellular and molecular life sciences : CMLS》2009,66(18):3053-3065
Mesenchymal stem cells (MSCs) have been shown to communicate with tumor cells. We analyzed the effect of human MSCs (hMSCs)
on breast cancer cells in three-dimensional cultures. By using GFP expression and immunohistochemistry, we show that hMSCs
invade 3D breast cancer cell aggregates. hMSCs caused breast cancer spheroids to become disorganized which was accompanied
by a disruption of cell–cell adhesion, E-cadherin cleavage, and nuclear translocation of E-cadherin, but not by epithelial/mesenchymal
transition or by an increase in ERK1/2 activity. In addition, hMSCs enhanced the motility of breast cancer cells. Inhibition
of ADAM10 (a disintegrin and metalloprotease 10), known to cleave E-cadherin, prevented both hMSC-mediated E-cadherin cleavage
and enhanced migration. Our data suggest that hMSCs interfere with cell–cell adhesion and enhance migration of breast cancer
cells by activating ADAM10. 相似文献
15.
Melinda Halasz Beata Polgar Gergely Berta Livia Czimbalek Julia Szekeres-Bartho 《Cellular and molecular life sciences : CMLS》2013,70(23):4617-4630
Invasiveness is a common feature of trophoblast and tumors; however, while tumor invasion is uncontrolled, trophoblast invasion is strictly regulated. Both trophoblast and tumor cells express high levels of the immunomodulatory progesterone-induced blocking factor (PIBF), therefore, we aimed to test the possibility that PIBF might be involved in invasion. To this aim, we used PIBF-silenced or PIBF-treated trophoblast (HTR8/Svneo, and primary trophoblast) and tumor (HT-1080, A549, HCT116, PC3) cell lines. Silencing of PIBF increased invasiveness as well as MMP-2,-9 secretion of HTR8/SVneo, and decreased those of HT-1080 cells. PIBF induced immediate STAT6 activation in both cell lines. Silencing of IL-4Rα abrogated all the above effects of PIBF, suggesting that invasion-related signaling by PIBF is initiated through the IL-4Rα/PIBF-receptor complex. In HTR-8/SVneo, PIBF induced fast, but transient Akt and ERK phosphorylation, whereas in tumor cells, PIBF triggered sustained Akt, ERK, and late STAT3 activation. The late signaling events might be due to indirect action of PIBF. PIBF induced the expression of EGF and HB-EGF in HT-1080 cells. The STAT3-activating effect of PIBF was reduced in HB-EGF-deficient HT-1080 cells, suggesting that PIBF-induced HB-EGF contributes to late STAT3 activation. PIBF binds to the promoters of IL-6, EGF, and HB-EGF; however, the protein profile of the protein/DNA complex is different in the two cell lines. We conclude that in tumor cells, PIBF induces proteins, which activate invasion signaling, while—based on our previous data—PIBF might control trophoblast invasion by suppressing proinvasive genes. 相似文献
16.
Leizerman I Avunie-Masala R Elkabets M Fich A Gheber L 《Cellular and molecular life sciences : CMLS》2004,61(16):2060-2070
The kinesin-related protein HsEg5 plays essential roles in mitotic spindle dynamics. Although inhibition of HsEg5 has been suggested as an aid in cancer treatment, the effects of such inhibition on human cells have not been characterized. Here we studied the effects of monastrol, an allosteric HsEg5 inhibitor, on AGS and HT29 cell lines and compared them to those of taxol. While both cell lines were similarly sensitive to taxol, AGS cells were more sensitive to monastrol. The differences in sensitivity were determined by the degree of inhibitory effect on cell proliferation, reversibility of monastrol-induced G2/M arrest, intracellular phenotypes and induction of apoptosis. In both cell lines, monastrol-induced apoptosis was accompanied by mitochondrial membrane depolarization and poly-ADP-ribose polymerase 1 cleavage. In AGS, but not HT29 cells, monastrol-induced apoptosis involved a prominent cleavage of procaspases 8 and 3. While in AGS cells, monastrol induced the formation of symmetric microtubule asters only, in HT29 cells, asymmetric asters were also formed, which may be related to specific HsEg5 functions in HT29 cells.Received 18 February 2004; received after revision 30 May 2004; accepted 16 June 2004 相似文献
17.
Shin JM Vagin O Munson K Kidd M Modlin IM Sachs G 《Cellular and molecular life sciences : CMLS》2008,65(2):264-281
Inhibition of gastric acid secretion is the mainstay of the treatment of gastroesophageal reflux disease and peptic ulceration;
therapies to inhibit acid are among the best-selling drugs worldwide. Highly effective agents targeting the histamine H2 receptor
were first identified in the 1970s. These were followed by the development of irreversible inhibitors of the parietal cell
hydrogen-potassium ATPase (the proton pump inhibitors) that inhibit acid secretion much more effectively. Reviewed here are
the chemistry, biological targets and pharmacology of these drugs, with reference to their current and evolving clinical utilities.
Future directions in the development of acid inhibitory drugs include modifications of current agents and the emergence of
a novel class of agents, the acid pump antagonists.
Received 30 May 2007; received after revision 15 August 2007; accepted 13 September 2007 相似文献
18.
Moshnikova AB Afanasyev VN Proussakova OV Chernyshov S Gogvadze V Beletsky IP 《Cellular and molecular life sciences : CMLS》2006,63(2):229-234
Currently, chemical bifunctional cross-linkers are regarded as promising therapeutic agents capable of affecting cell metabolism.
Depending on the nature of the active groups and on the length of their mediating spacer, these cross-linkers have been shown
to influence mitochondrial functions, the cell cycle and cell death. The current study was aimed to assay cellular effects
of a cross-linker with ‘zero’-length spacer, 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC). When added to cultures
of transformed cells, EDC induced a G2/M blockade followed by cell death. Analysis of the molecular targets revealed that
alteration of the cell cycle was caused by EDC-induced interchain cross-linking within double-stranded DNA. Administration
of EDC to animals with experimental tumors increased their life span. The analysis of tumor cells from EDC-treated mice showed
up-regulation of p21/WAF1, disturbance of tumor cell cytokinesis and, hence, cell death. Thus, both in vitro and in vivo, EDC exhibits cytotoxic activity, which may be of potential therapeutic use.
Received 15 August 2005; received after revision 23 September 2005; accepted 15 November 2005 相似文献
19.
Porcelli AM Ghelli A Iommarini L Mariani E Hoque M Zanna C Gasparre G Rugolo M 《Cellular and molecular life sciences : CMLS》2008,65(18):2943-2951
Human thyroid carcinoma XTC.UC1 cells harbor a homoplasmic frameshift mutation in the MT-ND1 subunit of respiratory complex
I. When forced to use exclusively oxidative phosphorylation for energy production by inhibiting glycolysis, these cells triggered
a caspase-independent cell death pathway, which was associated to a significant imbalance in glutathione homeostasis and a
cleavage of the actin cytoskeleton. Overexpression of the anti-apoptotic Bcl-2 protein significantly increased the level of
endogenous reduced glutathione, thus preventing its oxidation after the metabolic stress. Furthermore, Bcl-2 completely inhibited
actin cleavage and increased cell adhesion, but was unable to improve cellular viability. Similar effects were obtained when
XTC.UC1 cells were incubated with exogenous glutathione. We hence propose that Bcl-2 can safeguard cytoskeletal stability
through an antioxidant function.
Received 28 May 2008; received after revision 8 July 2008; accepted 29 July 2008 相似文献
20.
Suowen Xu Sayoko Ogura Jiawei Chen Peter J. Little Joel Moss Peiqing Liu 《Cellular and molecular life sciences : CMLS》2013,70(16):2859-2872
Lectin-like oxidized LDL (oxLDL) receptor-1 (LOX-1, also known as OLR-1), is a class E scavenger receptor that mediates the uptake of oxLDL by vascular cells. LOX-1 is involved in endothelial dysfunction, monocyte adhesion, the proliferation, migration, and apoptosis of smooth muscle cells, foam cell formation, platelet activation, as well as plaque instability; all of these events are critical in the pathogenesis of atherosclerosis. These LOX-1-dependent biological processes contribute to plaque instability and the ultimate clinical sequelae of plaque rupture and life-threatening tissue ischemia. Administration of anti-LOX-1 antibodies inhibits atherosclerosis by decreasing these cellular events. Over the past decade, multiple drugs including naturally occurring antioxidants, statins, antiinflammatory agents, antihypertensive and antihyperglycemic drugs have been demonstrated to inhibit vascular LOX-1 expression and activity. Therefore, LOX-1 represents an attractive therapeutic target for the treatment of human atherosclerotic diseases. This review aims to integrate the current understanding of LOX-1 signaling, regulation of LOX-1 by vasculoprotective drugs, and the importance of LOX-1 in the pathogenesis of atherosclerosis. 相似文献