LYSOSOMAL IRON ACCUMULATION AND TUBULAR DAMAGE IN RAT PUROMYCIN NEPHROSIS AND AGEING

1. Energy dispersive X-ray spectrometry was used to examine the relationship between proteinuria and increased urinary iron excretion, and structural and functional damage in puromycin nephrosis. 2. After 11–12 days rats treated with puromycin (10 mg/100g, i.v.i.) had greater proteinuria (211.6 ± 35.7 mg/day, mean ± s.e.m.) and urinary iron excretion (15.4 ± 2.2 μg/day) than salinetreated controls (14.5 ± 1.4 mg/day and 1.1 ± 0.2 μg/day, respectively, both P<0.001). 3. On day 13, mean lysosomal iron concentration of proximal tubular cells (306.6 ± 64.5 vs 11.9 ± 8.6 mg%, P<0.001), and proximal tubular cell damage assessed semi-quantitively (1.17 ± 0.10 vs 0.62 ± 0.10, P<0.001) were higher and creatinine clearance (0.15 ± 0.01 vs 0.29 ± 0.02 mL/min perg kidney weight, P<0.001) lower than in control rats. 4. At days 35, 60 and 360 there were no differences in any of the measured parameters between rats treated with puromycin or saline, and in both groups proteinuria, tissue damage and lysosomal iron concentration increased with time. 5. Lysosomal iron accumulation was the only independent predictor of both functional and structural damage. 6. In conclusion, the apparent association between proteinuria and tubulo-interstitial damage in puromycin nephrosis, and with ageing, is best explained by factors associated with accumulation of iron within lysosomes of proximal tubule cells.     

亚硒酸钠对荷Lewis肺癌小鼠癌组织和肝组织溶酶体的作用研究

用差速离心方法分离提取荷Lewis肺癌小鼠癌组织和肝组织富含溶酶体部分,并以溶酶体标志酶酸性磷酸酶(ACP)的游离酶和总酶活性比值作为观察溶酶体膜稳定性变化的指标,观察了亚硒酸钠对两种组织ACP酶活性和膜稳定性的影响。发现硒对癌组织和肝组织ACP活性的异常升高有抑制作用、稳定溶酶体膜,在癌瘤增殖前期作用明显(P<0.05)。提示这种拮抗效应与硒直接和间接的抗脂质过氧化有关。     

自体吞噬与类固醇激素分泌调节的关系

本实验用腹腔内给予下丘脑激素或类固醇激素的方法，造成大鼠睾丸间质细胞和肾上腺皮质束状带细胞处于分泌兴奋或抑制状态，对这两种分泌类固醇激素细胞中的溶酶体和自噬小体进行了超微结构、细胞化学和形态计量研究。结果表明，在类固醇激素分泌增多时，细胞中自体吞噬活动减弱；激素分泌减少时，自体吞噬活动加强。这一结果证明了细胞内的自体吞噬活动与类固醇激素的分泌调节有密切关系，自体吞噬是溶酶体参与激素分泌调节过程的一种重要方式。     

The Distribution of Synaptotagmin II in RBL-2H3 and Its Regulation on Exocytosis of Lysosomes in RBL-2H3

Synaptotagmin(Syt)constitutes a family of membrane-trafficking proteins,so far nearly 20 Syts have beendiscovered.Extensive work showed that synatotagmins were a potential Ca~(2+) sensor for regulated exocytosis.Thisstudy was to investigate the expression and location of synaptotagmin Ⅱ(Syt2)in RBL-2H3(RBL)and its role inregulating exocytosis of RBL.The expression of Syt2 in RBL was confirmed by Western blot.The recombinantexpression vector pEGFP-N1-Syt2 was constructed and transfected into RBL by electroporation,the stabletransfectant RBL-Syt2-S expressing fusion protein Syt2-EGFP were obtained and Syt2 was highly concentrated atplasma membrane with little detected in cytoplasm.To analyze the role of Syt2 during exocytosis of RBL,therelease of cathepsin D was assayed by immunoblotting.Compared with control,the release of cathepsin D byRBL-Syt2-S was markedly decreased.The results indicated that Syt2 played a negative regulation in exocytosis oflysosomes in RBL.Cellular & Molecular Immunology.2005;2(3):205-209.     

人体乳腺硬癌癌细胞器形态结构的定量研究

目的:区分乳腺正常细胞器和各期乳腺癌细胞器之间的差异,从而建立检查量化指标。方法:本文对女性乳腺硬癌癌细胞器线粒体,溶酶体的16个形态参数进行体视学统计分析。结果:发现癌细胞与正常细胞比较,其线粒体、溶酶体的体积、表面积和面数密度等形态参数存在高度显著差异和显著差异。结论:探讨了癌细胞的线粒体,溶酶体形态变异与功能之间的关系,为乳腺癌临床诊断提供了重要的定量依据。     

Effects of ultrasound,polyene antibiotics,and dyes on acid phosphatase activity of yeastlikeCandida fungal cells

Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 116, N ^o 9, pp. 272–274, September, 1993.     

Differential interactions of Streptococcus gordonii and Staphylococcus aureus with cultured osteoblasts

The impedance of normal osteoblast function by microorganisms is at least in part responsible for the failure of dental or orthopedic implants. Staphylococcus aureus is a major pathogen of bone, and exhibits high levels of adhesion and invasion of osteoblasts. In this article we show that the commensal oral bacterium Streptococcus gordonii also adheres to and is internalized by osteoblasts. Entry of S. gordonii cells had typical features of phagocytosis, similar to S. aureus, with membrane protrusions characterizing initial uptake, and closure of the osteoblast membrane leading to engulfment. The sensitivities of S. gordonii internalization to inhibitors cytochalasin D, colchicine and monensin indicated uptake through endocytosis, with requirement for actin accumulation. Internalization levels of S. gordonii were enhanced by expression of S. aureus fibronectin‐binding protein A (FnBPA) on the S. gordonii cell surface. Lysosomal‐associated membrane protein‐1 phagosomal membrane marker accumulated with intracellular S. aureus and S. gordonii FnBPA, indicating trafficking of bacteria into the late endosomal/lysosomal compartment. Streptococcus gordonii cells did not survive intracellularly for more than 12 h, unless expressing FnBPA, whereas S. aureus showed extended survival times (>48 h). Both S. aureus and S. gordonii DL‐1 elicited a rapid interleukin‐8 response by osteoblasts, whereas S. gordonii FnBPA was slower. Only S. aureus elicited an interleukin‐6 response. Hence, S. gordonii invades osteoblasts by a mechanism similar to that exhibited by S. aureus, and elicits a proinflammatory response that may promote bone resorption.     

Dysfunctional autophagy in Alzheimer’s disease: pathogenic roles and therapeutic implications

Neuronal autophagy is essential for neuronal survival and the maintenance of neuronal homeostasis. Increasing evidence has implicated autophagic dysfunction in the pathogenesis of Alzheimer’s disease (AD). The mechanisms underlying autophagic failure in AD involve several steps, from autophagosome formation to degradation. The effect of modulating autophagy is context-dependent. Stimulation of autophagy is not always beneficial. During the implementation of therapies that modulate autophagy, the nature of the autophagic defect, the timing of intervention, and the optimal level and duration of modulation should be fully considered.     

Autophagy： a double-edged sword for neuronal survival after cerebral ischemia

Evidence suggests that autophagy may be a new therapeutic target for stroke, but whether acti- vation of autophagy increases or decreases the rate of neuronal death is still under debate. This review summarizes the potential role and possible signaling pathway of autophagy in neuronal survival after cerebral ischemia and proposes that autophagy has dual effects.