Cadmium-induced apoptosis is mediated by the translocation of AIF to the nucleus in rat testes

Cadmium (Cd) is a highly toxic metal that affects a variety of cellular events, such as cell proliferation, differentiation and survival. Cd generates reactive oxygen species (ROS) that induce apoptosis. We previously demonstrated that Cd induces apoptosis in testicular germ cells and that apoptosis was prevented by the administration of ascorbic acid (AA), an ROS scavenger. However, little is known about the signaling pathways underlying Cd-induced apoptosis in rat testes. Here, we report that Cd-induced apoptosis in rat testes was associated with the translocation of apoptosis inducing factor (AIF) from mitochondria to the nucleus, and that this was prevented by treatment with AA. Cd-induced cleavage of poly ADP-ribose polymerase-1 (PARP-1), and this was also inhibited by treatment with AA. Taken together, these results suggest that Cd-induced ROS was responsible for the upregulation of PARP-1, the translocation of AIF to the nucleus, and apoptosis of testicular cells in rat testes.     

金属硫蛋白（MT）与男性不育患者精浆铅镉及精子参数的研究

目的探讨金属硫蛋白（Metallothionein,简称MT）与男性不育精浆铅镉、精子参数的关系。方法采用钨舟原子吸收光谱法检测患者口服金属硫蛋白前、后精浆铅Pb镉Cd的浓度;采用（computer aided semen anlysis,CASA）方法检测精子质量,分析各组数据间有无统计学意义。结果服用MT1-2个疗程前后进行统计学配对t检验：精子活率检测,密度、活率达到正常参考值的分别为46.8% P〈0.05统计学上有显著差异、34.78% P〈0.001统计学上有极显著差异。精子密度、精子活率的改善率分别为58.69% P〈0.05统计学上有显著差异、56.52%〈0.05统计学上有显著差异。结论口服MT后精子参数有不同程度的改善,对方怀孕11人占19.64%。     

jStudy of a Monte Carlo rearrangement model for the activity determination of electron-capture nuclides by means of liquid scintillation counting

A new Monte Carlo approach for the computation of the electron spectra of electron-capture nuclides is applied to obtain efficiencies in liquid scintillation counting for CIEMAT/NIST applications. The new method is applied to the radionuclides ¹⁰⁹Cd and ¹²⁵I by using a stochastic atomic rearrangement model, taking into account rearrangement processes including L-, M-, and N-subshells. The counting efficiencies were computed with the new code MICELLE which also comprises an approach for calculating the counting efficiency of a radionuclide in a gel phase sample. The calculated counting efficiencies are compared with experimental results.     

A rapid and transient ROS generation by cadmium triggers apoptosis via caspase-dependent pathway in HepG2 cells and this is inhibited through N-acetylcysteine-mediated catalase upregulation

Although reactive oxygen species (ROS) have been implicated in cadmium (Cd)-induced hepatotoxicity, the role of ROS in this pathway remains unclear. Therefore, we attempted to determine the molecular mechanisms relevant to Cd-induced cell death in HepG2 cells. Cd was found to induce apoptosis in the HepG2 cells in a time- and dose-dependent fashion, as confirmed by DNA fragmentation analysis and TUNEL staining. In the early stages, both rapid and transient ROS generation triggered apoptosis via Fas activation and subsequent caspase-8-dependent Bid cleavage, as well as by calpain-mediated mitochondrial Bax cleavage. The timing of Bid activation was coincided with the timing at which the mitochondrial transmembrane potential (MMP) collapsed as well as the cytochrome c (Cyt c) released into the cytosol. Furthermore, mitochondrial permeability transition (MPT) pore inhibitors, such as cyclosporin A (CsA) and bongkrekic acid (BA), did not block Cd-induced ROS generation, MMP collapse and Cyt c release. N-acetylcysteine (NAC) pretreatment resulted in the complete inhibition of the Cd-induced apoptosis via catalase upregulation and subsequent Fas downregulation. NAC treatment also completely blocked the Cd-induced intracellular ROS generation, MMP collapse and Cyt c release, indicating that Cd-induced mitochondrial dysfunction may be regulated indirectly by ROS-mediated signaling pathway. Taken together, a rapid and transient ROS generation by Cd triggers apoptosis via caspase-dependent pathway and subsequent mitochondrial pathway. NAC inhibits Cd-induced apoptosis through the blocking of ROS generation as well as the catalase upregulation.     

Toxicity and DNA damage in tobacco and potato plants growing on soil polluted with heavy metals

Heterezygous tobacco (Nicotiana tabacum var. xanthi) and potato (Solanum tuberosum var. Korela) plants were cultivated on soil from the site Strimice which is highly polluted with heavy metals and on nonpolluted soil from the recreational site Jezerí, both in North Bohemia, Czech Republic. The total content, the content of bioavailable, easily mobile, and potentially mobile components of heavy metals (Cd, Cu, Pb, and Zn) in the tested soils, and the accumulation of these metals in the above-ground biomass and roots of tested plants were analyzed by flame atomic absorption spectrometry or flameless atomic absorption spectrometry. The average tobacco leaf area and potato plant height were significantly reduced in plants growing on the polluted soil. We have measured the DNA damage in nuclei of leaves of both plant species using the Comet assay. A small but significant increase in DNA damage was noted in plants growing on the polluted soil versus controls. As the tobacco and potato plants with increased DNA damage were severely injured (inhibited growth, distorted leaves), this increase may be associated with necrotic or apoptotic DNA fragmentation. No increase in the frequency of somatic mutation was detected in tobacco plants growing on the polluted soil. Thus, the polluted soil probably induced toxic but not genotoxic effects on tobacco and potato plants.     

Cadmium induces apoptotic cell death in WI 38 cells via caspase-dependent Bid cleavage and calpain-mediated mitochondrial Bax cleavage by Bcl-2-independent pathway

Previous reports have demonstrated that cadmium (Cd) may induce cell death via apoptosis, but the mechanism responsible for cellular death is not clear. In this study, we investigated the signaling pathways implicated in Cd-induced apoptosis in lung epithelial fibroblast (WI 38) cells. Apoptotic features were observed using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay, propidium iodide staining and DNA laddering. A treatment of cadmium caused the caspase-8-dependent Bid cleavage, the release of cytochrome c (Cyt c), activation of caspase-9 and -3, and PARP cleavage. A caspase-8 specific inhibitor prevented the Bid cleavage, caspase-3 activation and cell death. Alternatively, we observed that full-length Bax was cleaved into 18-kDa fragment (p18/Bax); this was initiated after 12 h and by 36 h the full-length Bax protein was totally cleaved to the p18/Bax, which caused a drastic release of Cyt c from mitochondria. The p18/Bax was detected exclusively in the mitochondrial fraction, and it originated from mitochondrial full-length Bax, but not from the cytosol full-length Bax. Cd also induced the activation of the mitochondrial 30-kDa small subunit of calpain that was preceded by Bax cleavage. Cd induced the upregulation of Bcl-2 and the degradation of p53 protein. N-acetyl cysteine effectively inhibited the Cd-induced DeltaPsim reduction, indicating ROS acts upstream of mitochondrial membrane depolarization. Taken together, our results suggest that Cd-induced apoptosis was thought to be mediated at least two pathways; caspase-dependent Bid cleavage, and the other is calpain-mediated mitochondrial Bax cleavage. Moreover, we found that the function of Bid and Bax was not dependent of Bcl-2, and that ROS can also contribute in the Cd-induced cell death.     

氯化镉对大鼠睾丸超微结构的损伤

目的:观察氯化镉(CdCl2)对大鼠睾丸组织超微结构的损伤。方法:18只成年雄性SD大鼠随机均分为对照组(A组)与2个CdCl2实验组,实验组分别腹腔注射CdCl20.2mg/kg(B组)和0.8mg/kg(C组)2周。应用透射电镜观察睾丸超微结构的变化。结果:与对照组相比,B组和C组普遍观察到曲细精管基膜变薄,电子密度低,厚薄不均,呈波浪式皱褶;睾丸间质细胞、支持细胞、精原细胞分别有部分细胞出现胞质空泡,线粒体水肿、空泡化,内质网扩张、空泡化,溶酶体增多。C组部分精原细胞核固缩,少数精子部分顶体脱离细胞核。结论:CdCl2染毒可导致大鼠睾丸间质细胞、基膜、支持细胞、精原细胞和精子发生超微结构的改变,剂量增加时病理改变加重。     

An ultrastructural,immunohistochemical, and cytogenetical study of a monophasic pulmonary synovial sarcoma: implications of the frequent ultrastructure of oligocilia and concentric membranous bodies with positive immunostaining for VS38c and MEF2

A rare case of a monophasic pulmonary synovial sarcoma is reported. A 44-year-old Japanese man underwent lower lobectomy for a nodular mass in his right lung. Immunohistochemical study of the excised primitive spindle cell sarcoma revealed occasional positive stains by hitherto reported antigens of S-100, cytokeratin 7, high molecular weight cytokeratin (34betaE12), pankeratin (AE1/AE3), and EMA, which were helpful for the differential diagnosis of other spindle cell sarcomas. Furthermore, positive immunostains for MEF2, VS38c (plasma cell antigen), and bcl-2 were rather significant findings in the present case. The definitive evidence that molecular genetic analysis showed a clonal single electrophoretic band of SYT-SSX mutated chimera gene was conclusive for the pathological diagnosis. The implications of the frequently seen ultrastructure of oligocilia and concentric membranous bodies with positive stains for VS38c and MEF2 are discussed. In the difficult pathological diagnosis of a rare and undifferentiated type of sarcoma with unusual clinicopathological features generated at an unusual site, comprehensive ultrastructural, immunohistochemical, and cytogenetic studies will lead to the correct pathological diagnosis and elucidate the detailed characteristics of the tumor.     

Adult hypocellular acute leukaemia with lymphoid differentiation

The rare hypocellular variants of acute leukemia (AL) previously also termed smouldering leukemia, almost always exhibit myeloid differentiation. Very rare cases of hypocellular AL with lymphoid differentiation have been reported, usually in children. This paper describes two cases (an 87-year-old woman and a 79-year-old man) in whom the blood findings were suggestive of AL. Paraffin-embedded bone marrow biopsy specimens revealed similar findings in both patients: there was severe hypocellularity, the cells of normal hemopoiesis were greatly reduced in number, and there was a diffuse increase in blast cells, which represented more than 50% of nucleated marrow cells. The blasts coexpressed TdT and CD34 and were negative for myeloperoxidase, CD117, CD68 and naphthol AS-D chloroacetate esterase. For the first time immunohistochemical Pax-5/CD34 doublestainings are provided, which revealed the blasts in one case to coexpress Pax-5 and CD34. All the blasts were CD79a-positive and 20% were also CD10-positive. In the other case, 20% of the blasts were CD79a-positive, 30% coexpressed Pax-5 and CD34 by doublestaining, and showed a clonal rearrangement of the immunoglobulin heavy chain gene. Thus a diagnosis of AL of lymphoid lineage, hypocellular variant, was made on the basis of immunohistochemical findings. The clinical course appears to be similar to that of hypocellular AML, as neither patient has developed overt leukemia during the one-year follow-up period.