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1.
In a biological microenvironment, free fatty acids (FFA) as ubiquitous biological molecules might interact with nanoparticles (NPs) and consequently change the toxicological responses. However, whether the chemical structures of FFA could influence their interactions with NPs remain unknown. This study investigated the interactions between ZnO NPs and saturated or unsaturated FFA (complexed to BSA), namely stearic acid (SA, C18:0), oleic acid (OA, C18:1), and α-linolenic acid (ALA, C18:3). It was shown that BSA, SA, OA, and ALA increased the atomic force microscope (AFM) heights as well the polydispersity index (PDI) of ZnO NPs. BSA modestly protected THP-1 macrophages from ZnO NP exposure, whereas OA and ALA led to relatively less cyto-protective effects of BSA. Moreover, only co-exposure to ZnO NPs and SA significantly promoted the release of interleukin-8. BSA, SA, OA, and ALA equally changed intracellular ROS and Zn ions associated with ZnO exposure, but co-exposure to ZnO NPs and OA/ALA particularly activated the expression of endoplasmic reticulum stress-apoptosis genes. In combination, these results showed that FFA could influence the colloidal aspects and toxicological signaling pathway of ZnO NPs, which is dependent on the number of unsaturated bonds of FFA.  相似文献   
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Metastatic melanoma is the most deadly skin neoplasm in the United States. Outcomes for this lethal disease have improved dramatically due to the use of both targeted and immunostimulatory drugs. Immunogenic cell death (ICD) has emerged as another approach for initiating antitumor immunity. ICD is triggered by tumor cells that display damage-associated molecular patterns (DAMPs). These DAMP molecules recruit and activate dendritic cells (DCs) that present tumor-specific antigens to T cells which eliminate neoplastic cells. Interestingly, the expression of DAMP molecules occurs in an endoplasmic reticulum (ER) stress-dependent manner. We have previously shown that ER stress was required for the cytotoxic activity of the endocannabinoid metabolite, 15-deoxy, Δ12,14 prostamide J2 (15dPMJ2). As such, the current study investigates whether 15dPMJ2 induces DAMP signaling in melanoma. In B16F10 cells, 15dPMJ2 caused a significant increase in the cell surface expression of calreticulin (CRT), the release of ATP and the secretion of high-mobility group box 1 (HMGB1), three molecules that serve as surrogate markers of ICD. 15dPMJ2 also stimulated the cell surface expression of the DAMP molecules, heat shock protein 70 (Hsp70) and Hsp90. In addition, the display of CRT and ATP was increased by 15dPMJ2 to a greater extent in tumorigenic compared to non-tumorigenic melanocytes. Consistent with this finding, the activation of bone marrow-derived DCs was upregulated in co-cultures with 15dPMJ2-treated tumor compared to non-tumor melanocytes. Moreover, 15dPMJ2-mediated DAMP exposure and DC activation required the electrophilic cyclopentenone double bond within the structure of 15dPMJ2 and the ER stress pathway. These results demonstrate that 15dPMJ2 is a tumor-selective inducer of DAMP signaling in melanoma.  相似文献   
4.
Inflammation plays a critical role in the development of ventilator-induced lung injury (VILI). Endoplasmic reticulum (ER) stress is associated with a variety of diseases through the modulation of inflammatory responses. However, little is known about how ER stress is implicated in VILI. In this study, murine mechanical ventilation models were constructed. Total protein and inflammatory cytokines were measured in bronchoalveolar lavage fluid (BALF), and lung tissue injury was assessed by histology. Our data revealed that mice subjected to high tidal ventilation (TV) for 4 h showed more severe pulmonary edema and inflammation than those of mice with spontaneous breathing and low TV-treatment. In addition, the high TV-treated animals upregulated the ER stress markers GRP78, CHOP, p-IRE1α, TRAF2, and p-NF-κB expression at both the mRNA and protein levels in lung tissue. Administration of thapsigargin exacerbated the histological changes, inflammation and expression of GRP78 and CHOP after high TV, but treatment with ER stress and IRE1α kinase inhibitors attenuated the pathological damage and downregulated the high expression of GRP78, CHOP, p-IRE1α, TRAF2, and p-NF-κB, suggesting that ER stress is involved in VILI though the IRE1α/TRAF2/NF-κB signaling pathway in mice.  相似文献   
5.
. We have estimated sarcoplasmic reticulum calcium content using rapid application of caffeine on voltage clamped, isolated guinea-pig ventricular myocytes. Caffeine induces the release of calcium from the sarcoplasmic reticulum and this calcium is extruded from the cells by the sarcolemmal Na/Ca exchange. Integrating the inward Na/Ca exchange current thus allows estimations of sarcoplasmic reticulum calcium content. Ventricular myocytes were stimulated to reach new steady-states by action potential voltage clamps of varying duration. Once contractile steady-state had been reached caffeine was rapidly applied in place of the next action potential and sarcoplasmic reticulum calcium content measured. Prolonging the action potential duration increased sarcoplasmic reticulum calcium content and vice-versa. This calcium loading may underlie the positive inotropic effect of increased action potential duration. Received: 11 July 1996 / Received after revision: 15 October 1996 / Accepted: 26 November 1996  相似文献   
6.
Background: The direct effect of halothane on vascular smooth muscle is mediated in part via its effects on the sarcoplasmic reticulum (SR). Little information is available concerning the effects of other volatile anesthetics including isoflurane and sevoflurane, whose vascular effects differ from those of halothane. The aim of the present study was to compare the effects of halothane, isoflurane and sevoflurane on the SR by testing the contraction induced by caffeine in vascular smooth muscle. Methods: Rings without endothelium from isolated canine mesenteric artery were mounted in physiological saline solution (PSS) for isometric tension recording. After complete depletion of Ca2+ from the SR by adding 35 mM caffeine, the rings were exposed to normal Ca2+ containing PSS (Ca2+ loading), to Ca2+-free PSS for 10 min, and then to 15 mM caffeine to induce contraction. Anesthetics were administered during Ca2+ loading, the Ca2+-free phase and simultaneously with caffeine administration. Results: Halothane (0.5-2%) attenuated the caffeine-induced contraction of canine mesenteric artery when administered during Ca2+ loading in the SR (P<0.001), whereas isoflurane and sevoflurane (1–4%) failed to affect the contraction. When given simultaneously with caffeine, halothane (1–2%) potentiated the caffeine-induced contraction (P<0.05), but isoflurane and sevoflurane had no effect. When given before caffeine administration, halothane (0.5-2%), isoflurane (24%) and sevoflurane (4%) all potentiated the caffeine-induced contraction (P<0.05). Conclusion: It has been shown that halothane not only potentiates caffeine- induced Ca2+ release from the SR, but also induces contraction by releasing Ca2+ from the SR. We conclude that halothane decreases Ca2+ accumulation in the SR while exerting facilitative and additive effects on caffeine-induced Ca2+ release from the SR when applied before caffeine administration and simultaneously with caffeine, respectively, whereas isoflurane and sevoflurane lack both the ability to decrease Ca2+ accumulation and an additive effect on caffeine-induced Ca2+ release from the SR, but are able to facilitate Ca2+ release by caffeine.  相似文献   
7.
兔膀胱出口部分梗阻所致逼尿肌超微结构的改变   总被引:4,自引:0,他引:4  
目的 观察兔膀胱出口部分梗阻后逼尿肌细胞超微结构的改变。 方法 建立雄性兔膀胱出口部分梗阻动物模型 ,利用透射电镜观察其逼尿肌细胞内超微结构 ,应用ImagineTool图像分析软件检测粗面内质网面积和线粒体密度。 结果 梗阻组逼尿肌细胞内单位面积平均 1 1 5 .2 8μm2 ,胞质中粗面内质网面积 (5 .377± 2 .31 8) μm2 ,较对照组的 (0 .476± 0 .31 9) μm2 明显扩大 ;线粒体相对密度为 1 .0 2 7± 0 .0 64 ,较对照组的 0 .830± 0 .0 58明显下降 ,P均 <0 .0 1。 结论 膀胱出口部分梗阻后逼尿肌细胞内质网扩张 ,提示其合成蛋白质功能增强 ,从而引起膀胱壁增厚 ;而线粒体水肿明显 ,密度下降 ,提示逼尿肌细胞能量代谢障碍 ,导致其收缩功能下降  相似文献   
8.
应用电子自旋共振波谱仪(ESR)直接检测了缺血-再灌注兔心肌肌浆网自由基的变化,以探讨肌质网系统与氧自由基的关系。实验中将20只兔随机分为再灌注对照组、超氧化物歧化酶(SOD)组、ATP-氯化镁组和人参皂甙Re组。实验结果,g值2.0046处为半醌自由基波谱,其相对浓度各组依次为78.94±2.126,14.46±2.86,20.65±7.65,14.66±3.67(x±SD),对照组与用药组均有显著性差异(P<0.05),表明缺血-再灌注兔心肌肌浆网产生大量的自由基,用ESR可以直接检测到半醌自由基,外源性高能磷酸盐制剂ATP-氯化镁及人参皂甙Re与超氧化物歧化酶一样,发挥清除兔心肌肌浆网自由基的作用。  相似文献   
9.
We studied the histological and ultrastructural changes in the liver and alterations in the liver test results before, during, and after treatment with human interferon- from five patients with hepatitis B e antigen-positive chronic active hepatitis. A daily dose of 3×106 to 6×106 units of interferon- was given intravenously for four weeks. The total index of periportal and portal inflammation, intralobular degeneration, and focal necrosis before treatment was decreased significantly six months after treatment (P<0.05). Ultrastructurally, the structure of endoplasmic reticulum was irregularly shaped or fragmentally decreased during treatment, but these disappeared six or 12 months after treatment. Glycogen particles diminished greatly during treatment. The alanine aminotransferase concentrations in these patients increased during treatment. Serum albumin and cholinesterase levels decreased significantly at the fourth week of treatment (P<0.01) and at the third day (P<0.01) to the second week (P<0.05) of treatment, respectively. These results suggest that interferon- injures endoplasmic reticulum and glycogen areas and damages the cholinesterase activity in the early stage of treatment and protein synthesis in patients with hepatitis B e antigen-positive chronic active hepatitis.  相似文献   
10.
The present study has focused mainly on microenvironmental aspects of the thymus from a 17-year-old female patient suffering from myasthenia gravis. The most striking lightmicroscopic feature was again the well known presence of lymphoid follicular hyperplasia. Ultrastructurally, the configuration, cellular composition and fine structure were to a large extent the same as in other, peripheral lymphoid organs. Cells showing the typical morphologic characteristics of fibroblastic reticulum cells, which are most probably precursors of dendritic reticulum cells, were observed within germinal centers. Additionally the morphology of the unaffected medulla and corticomedullary region was studied, thereby paying particular attention to the structural changes of interdigitating cells. These contained frequently Birbeck granules, which have not been described before in human thymus.  相似文献   
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