N-Acetylcysteine ameliorates lipopolysaccharide-induced organ damage in conscious rats

Lipopolysaccharide is strongly associated with septic shock, leading to multiple organ failure. It can activate monocytes and macrophages to release proinflammatory mediators such as tumor necrosis factor- (TNF-), interleukin-1 (IL-1), and nitric oxide (NO). The present experiments were designed to induce endotoxin shock by an intravenous injection ofKlebsiella pneumoniae lipopolysaccharide (LPS, 10 mg/kg) in conscious rats. Arterial pressure and heart rate (HR) were continuously monitored for 48 h after LPS administration. N-Acetyl-cysteine was used to study its effects on organ damage. Biochemical substances were measured to reflect organ functions. Biochemical factors included blood urea nitrogen (BUN), creatinine (Cre), lactic dehydrogenase (LDH), creatine phosphokinase (CPK), aspartate transferase (GOT), alanine transferase (GPT), TNF-, IL-1, methyl guanidine (MG), and nitrites/nitrates. LPS caused significant increases in blood BUN, Cre, LDH, CPK, GOT, GPT, TNF-, IL-1, MG levels, and HR, as well as a decrease in mean arterial pressure and an elevation of nitrites/nitrates. N-Acetylcysteine suppressed the release of TNF-, IL-1, and MG, but enhanced NO production. These actions ameliorate LPS-induced organ damage in conscious rats. The beneficial effects may suggest a potential chemopreventive effect of this compound in sepsis prevention and treatment.     

肾素-血管紧张素系统在调节肾脏活动和慢性肾功能不全中的作用

一、肾内RAS的组成、生物学特征及肾内分布;(一)有关RAS的研究进展;(二)肾脏组织局部的RAS;(三)AngⅡ受体的亚型及其在肾内的分布;二、AngⅡ对肾脏血流动力学的影响;三、AngⅡ对肾脏的非血流动力学效应;(一)AngⅡ的促生长作用及促纤维生成效应;(二)AngⅡ作为促炎症因子的作用;四、有关RAS在肾功能不全中的临床研究     

利用阵列分析水稻AP2/EREBP 家族基因的表达特性

AP2/EREBP蛋白是广泛存在于高等植物中的且包含AP2/EREBP功能域的重要转录因子家族, 通常可分为包含单功能域的EREBP类蛋白和包含两个功能域的AP2类蛋白, 它们的功能涉及植物生长发育调控和对逆境应答等许多方面。据预测,水稻基因组编码150个左右的AP2/EREBP 家族成员, 但目前绝大多数蛋白的功能仍不清楚。为了解这些基因在水稻不同器官中的表达特性, 我们以AP2/EREBP功能域的氨基酸序列为基础, 从水稻基因组数据库中搜索到12个AP2类以及20个EREBP类预测基因, 利用PCR扩增的编码区序列制备了这些预测基因的macro-array。 以幼芽、幼根、幼叶、颖花和灌浆期成熟叶的 cDNA为探针, 杂交分析结果显示: 不同AP2类预测基因之间的表达量差别较大, 但同一个基因在不同器官中表达量基本一致; 与此不同的是, 大部分EREBP类预测基因在幼根和成熟叶片中表达量较高, 而在幼芽和幼叶中表达量较低。这些预测基因的表达模式可能与它们的功能密切相关。     

A visit to the zoos and aquariums in Northern Japan

For their trip to the National Parks in Hokkaido the authors also included in their schedule visits to the zoos and aquariums in Northern Japan. Their tight scheduled tour started at the Aquamarine Fukushima, which was after the large tsunami rebuilt and re-opened in July 2011. They continued with a visit to the Kamo Aquarium, which is famous for its unique and large jellyfish exhibition. On Hokkaido Island they visited the smaller zoos in Kushiro and Obihiro with a good collection of native Hokkaido animal species. Included was also the Asahiyama Zoo, which is at the moment one of the most popular zoos in Japan. It is well-known for its innovative enclosures for seals and penguins. The Sapporo Maruyama Zoo and the Chitose Salmon Aquarium were the last highlights of this tour. The themes and animal collections of these different zoos and aquariums are described. The general situation for the northern zoos and aquariums is quite different compared to the institutions in the southern parts of the country and entirely to the zoos in the large city areas like Tokyo, Osaka and Nagoya. Here in the northern zoos and aquariums many native animal species and subspecies are kept and often successfully bred.     

Pseudo-random mating systems for 3-allele loci

A random mating population attains equilibrium by the Hardy-Weinberg law. By demonstrating some simple examples for 2-allele loci, Li (1988) showed that a nonrandom mating population of certain mating patterns may also attain equilibrium. He called such a type of population a pseudo-random mating population. Tai (1990), then, gave a generalized representation of these pseudo-random mating systems. In this paper the clear patterns of pseudo-random mating behavior for a 3-allele locus are derived. Both autosomal and sex-linked systems are discussed. The study of these mating patterns provides a way to understand the complicated mating system of a population, which usually is only with difficulty realized through sampled individuals from that population.     

Slit2 Inactivates GSK3β to Signal Neurite Outgrowth Inhibition

Slit molecules comprise one of the four canonical families of axon guidance cues that steer the growth cone in the developing nervous system. Apart from their role in axon pathfinding, emerging lines of evidence suggest that a wide range of cellular processes are regulated by Slit, ranging from branch formation and fasciculation during neurite outgrowth to tumor progression and to angiogenesis. However, the molecular and cellular mechanisms downstream of Slit remain largely unknown, in part, because of a lack of a readily manipulatable system that produces easily identifiable traits in response to Slit. The present study demonstrates the feasibility of using the cell line CAD as an assay system to dissect the signaling pathways triggered by Slit. Here, we show that CAD cells express receptors for Slit (Robo1 and Robo2) and that CAD cells respond to nanomolar concentrations of Slit2 by markedly decelerating the rate of process extension. Using this system, we reveal that Slit2 inactivates GSK3β and that inhibition of GSK3β is required for Slit2 to inhibit process outgrowth. Furthermore, we show that Slit2 induces GSK3β phosphorylation and inhibits neurite outgrowth in adult dorsal root ganglion neurons, validating Slit2 signaling in primary neurons. Given that CAD cells can be conveniently manipulated using standard molecular biological methods and that the process extension phenotype regulated by Slit2 can be readily traced and quantified, the use of a cell line CAD will facilitate the identification of downstream effectors and elucidation of signaling cascade triggered by Slit.     

Hyperosmolarity enhanced susceptibility to renal tubular fibrosis by modulating catabolism of type I transforming growth factor‐β receptors

Hyperosmolarity plays an essential role in the pathogenesis of diabetic tubular fibrosis. However, the mechanism of the involvement of hyperosmolarity remains unclear. In this study, mannitol was used to evaluate the effects of hyperosmolarity on a renal distal tubule cell line (MDCK). We investigated transforming growth factor‐β receptors and their downstream fibrogenic signal proteins. We show that hyperosmolarity significantly enhances the susceptibility to exogenous transforming growth factor (TGF)‐β1, as mannitol (27.5 mM) significantly enhanced the TGF‐β1‐induced increase in fibronectin levels compared with control experiments (5.5 mM). Specifically, hyperosmolarity induced tyrosine phosphorylation on TGF‐β RII at 336 residues in a time (0–24 h) and dose (5.5–38.5 mM) dependent manner. In addition, hyperosmolarity increased the level of TGF‐β RI in a dose‐ and time‐course dependent manner. These observations may be closely related to decreased catabolism of TGF‐β RI. Hyperosmolarity significantly downregulated the expression of an inhibitory Smad (Smad7), decreased the level of Smurf 1, and reduced ubiquitination of TGF‐β RI. In addition, through the use of cycloheximide and the proteasome inhibitor MG132, we showed that hyperosmolarity significantly increased the half‐life and inhibited the protein level of TGF‐β RI by polyubiquitination and proteasomal degradation. Taken together, our data suggest that hyperosmolarity enhances cellular susceptibility to renal tubular fibrosis by activating the Smad7 pathway and increasing the stability of type I TGF‐β receptors by retarding proteasomal degradation of TGF‐β RI. This study clarifies the mechanism underlying hyperosmotic‐induced renal fibrosis in renal distal tubule cells. J. Cell. Biochem. 109: 663–671, 2010. © 2010 Wiley‐Liss, Inc.