Dysfunction of kidney endothelium after ischemia/reperfusion and its prevention by mitochondria-targeted antioxidant

One of the most important pathological consequences of renal ischemia/reperfusion (I/R) is kidney malfunctioning. I/R leads to oxidative stress, which affects not only nephron cells but also cells of the vascular wall, especially endothelium, resulting in its damage. Assessment of endothelial damage, its role in pathological changes in organ functioning, and approaches to normalization of endothelial and renal functions are vital problems that need to be resolved. The goal of this study was to examine functional and morphological impairments occurring in the endothelium of renal vessels after I/R and to explore the possibility of alleviation of the severity of these changes using mitochondria-targeted antioxidant 10-(6′-plastoquinonyl)decylrhodamine 19 (SkQR1). Here we demonstrate that 40-min ischemia with 10-min reperfusion results in a profound change in the structure of endothelial cells mitochondria, accompanied by vasoconstriction of renal blood vessels, reduced renal blood flow, and increased number of endothelial cells circulating in the blood. Permeability of the kidney vascular wall increased 48 h after I/R. Injection of SkQR1 improves recovery of renal blood flow and reduces vascular resistance of the kidney in the first minutes of reperfusion; it also reduces the severity of renal insufficiency and normalizes permeability of renal endothelium 48 h after I/R. In in vitro experiments, SkQR1 provided protection of endothelial cells from death provoked by oxygen–glucose deprivation. On the other hand, an inhibitor of NO-synthases, L-nitroarginine, abolished the positive effects of SkQR1 on hemodynamics and protection from renal failure. Thus, dysfunction and death of endothelial cells play an important role in the development of reperfusion injury of renal tissues. Our results indicate that the major pathogenic factors in the endothelial damage are oxidative stress and mitochondrial damage within endothelial cells, while mitochondria-targeted antioxidants could be an effective tool for the protection of tissue from negative effects of ischemia.     

Do mitochondria have an immune system?

The question if mitochondria have some kind of immune system is not trivial. The basis for raising this question is the fact that bacteria, which are progenitors of mitochondria, do have an immune system. The CRISPR system in bacteria based on the principle of RNA interference serves as an organized mechanism for destroying alien nucleic acids, primarily those of viral origin. We have shown that mitochondria are also a target for viral attacks, probably due to a related organization of genomes in these organelles and bacteria. Bioinformatic analysis performed in this study has not given a clear answer if there is a CRISPR-like immune system in mitochondria. However, this does not preclude the possibility of mitochondrial immunity that can be difficult to decipher or that is based on some principles other than those of CRISPR.     

Mechanisms of inflammatory injury of renal tubular cells in a cellular model of pyelonephritis

Previously, we have assembled a cellular model of pyelonephritis which contains a primary culture of renal tubular epithelial cells, mononuclear leukocytes, and bacterial lysate or lipopolysaccharide. After cocultivation of renal cells with leukocytes and bacterial lysate, proinflammatory changes were observed in the renal cells, followed by nitrosative and oxidative stress and cell death. The interaction of bacterial antigens not only with leukocytes, but also with epithelial cells of the renal tubules, was partially mediated by signaling pathways involving Toll-like receptors (TLR2 and TLR4). Activation of these receptors led to increased levels of oxidative stress and synthesis of proinflammatory cytokines (TNF, IL-6, IL-1α) in the renal epithelium, while TLR4 blockade decreased the severity of these processes. Apart from the fact that activation of inflammatory signaling in response to bacterial antigens is observed directly in the renal cells, the presence of leukocytes significantly amplifies the inflammatory response as measured by the level of cytokines generated in the ensemble. In the presence of activated leukocytes, higher expression of TLR2 on the surface of renal cells was observed in response to exposure to bacterial components, which might explain the increased inflammatory response in the presence of leukocytes. The synthesis of IL-1α in the epithelial cells of the renal tubules in this inflammatory model leads to its accumulation in the nuclei, which has been reduced by the TLR4 antagonist polymyxin. TLR2 agonists also led to increased levels of IL-1α. The elevation in the content of IL-1α in nuclei was accompanied by increased acetylation of nuclear proteins, which has been reduced to control values after exposure to protective agents (Trolox, mitochondria-targeted antioxidant SkQR1 or LiCl). The high level of acetylation of histones is probably regulated by proinflammatory cytokines, and to some extent it is a marker of inflammation, which can indirectly be reduced by protective agents.     

Evolution of the structural and cytochemical organization of the taste buds in vertebrates

Ultrastructural and cytochemical organization of the receptors, supporting and basal cells of vertebrate taste buds are described. The receptor cells of all the vertebrates are characterized by single large microvillar process, well developed smooth endoplasmic reticulum and synaptic contacts with afferent and efferent nerve endings. A number of enzymes and acid mucopolysaccharides were demonstrated on the membrane of the microvillar process. At the synaptic area, AChE activity and monoamines are revealed. Besides, less numerous type of the receptor cells with several smaller microvillar processes are described in the taste buds. The supporting cells are characterized by numerous secretory granules and bundles of longitudinally oriented tonofibrils. The basal cells lie on the basal membrane and have no contact with the environment. Possible contribution of each type of the taste bud cells into gustation is discussed.     

Brain enzyme activity in irradiated sympathectomized rats

The results are reviewed from studies of activity of hexokinase (2.7.1.1.EC), dehydrogenase glucose-6-phosphate (1.1.1.49 EC), and cholinesterase (3.1.1.7 EC) in subcellular fractions of rat brain at the background of chemical sympathectomy induced by long-term administration of guanethidine and subsequent irradiation with a dose of 7 Gy. In conditions of sympathectomy, the enzyme activity is inhibited; in irradiated sympathectomized rats, activity of hexokinase and cholinesterase increases to reach the level of that of intact animals while dehydrogenase remains inhibited.     

Investigation of ribosomes of E. coli and T. maritima by atomic force microscopy

Subunits 70S, 50S, and 30S of ribosomes of E. coli and T. maritima have been studied by atomic force microscopy. A considerable heterogeneity of structures was visualized when 70S and 30S subunits were sorbed on mica. The linear size and the height of molecules were estimated. It was found that the heights of ribosomes of E. coli and T. maritima substantially differ. The average height of 70S ribosomes of E. coli was 9.4 + 0.01 nm and that of T. maritima was 10.35 +/- 0.02 nm. The differences in the dimensions were probably determined by special organization of the mobile ribosomal element the L7/L12-stalk.     

克拉玛依市2008年麻疹监测与控制情况分析

分析克拉玛依市麻疹流行状况及预防控制措施,为消除麻疹提供依据。采用描述流行病学分析方法,对2008年克拉玛依市麻疹资料进行分析。结果显示,克拉玛依市2008年麻疹发病率为38.83/10万(138/355381),呈高度散发,较2007年有所上升。发病高峰在3～5月,发病数占全年的83.33%。年龄分布大年龄组高于小年龄组,>20岁年龄组病例占50.00%,<1岁病例占18.84%;流动人口发病占51.11%。应切实提高麻疹常规免疫接种率和做好入托、入学儿童查验预防接种证工作,加强麻疹监测,提高实验室确诊病例的比例。