Sensory transduction and the mammalian epidermis

This paper constitutes, in its main intent, an introduction to the mammalian epidermis as a surface for biosensor applications. In particular, the structure and function of the epidermis of the newborn rat are examined as a model for studies of the human state. Data are presented illustrating an anisotropic organization of the dorsal surface of the neonatal rodent with regard to line of tension and thermal gradients. The dependence of the mechanical properties of the epidermis upon calcium is examined by means of an in-vitro assay of epidermal retraction. The potential role of keratin tonofilaments as piezoelectric and pyroelectric elements in the epidermis is introduced and the spatial alignment of these macromolecular arrays is demonstrated to be a function of physiological tensions. These findings are discussed in the context of noninvasive epidermal sensors utilized to understand mechanisms of sensory development and physiological regulation. Optoelectronic (infrared) imaging of the dorsal temperature field and the alteration in this field by treatment with epidermal growth factor are presented as examples of this methodologic approach. It is concluded that a detailed examination of the material and physical properties of mammalian epidermis is a reasonable goal of biosensor development and research. Hypothetically, such studies may reveal important molecular and cellular mechanisms by which sensory data are transmitted or transduced at the organism-environmental interface.     

预热处理对缺血心肌的保护作用及蛋白激酶C信号转导通路机制

缺血心肌的保护一直是心血管研究领域的热点问题。目前,除了继续从外源性药物途径进行研究外,有一个崭新的领域越来越受到人们的重视,即通过心肌细胞本身的内源性抗损伤能力,产生自身保护作用来减轻缺血的损害。研究发现,适当的预处理可以有效调动该保护机制。本文就近年来发展较快的预热处理(HP)对缺血心肌的保护作用及其蛋白激酶C(PKC)信号转导通路机制作一简要概述。     

Sensory transduction in the gliding bacterium Myxococcus xanthus

Sensory transduction in the gliding bacterium Myxococcus xanthus is mediated by the frz genes. These genes are homologous to the chemotaxis genes of enteric bacteria and control the rate of cell reversal during gliding. Sensory transduction is hypothesized to involve the recognition of substances present in the medium at the cell surface and the subsequent stimulation of a cytoplasmic methyl-accepting protein, FrzCD. Phosphorylation of FrzE is also involved in the sensory transduction pathway. Despite the similarities between the chemotaxis proteins of enteric bacteria and M. xanthus Frz proteins, fundamental differences exist between these different bacteria in terms of the ability of cells to recognize and respond to substances in their environment. The mechanism of directional switching and the nature of the gliding motor remain obscure. It is hoped that the study of the interaction of the Frz proteins will allow greater understanding of these problems.     

Wnt signal transduction and the formation of the myocardium

Soon after fertilization, vertebrate embryos grow very rapidly. Thus, early in gestation, a sizeable yet underdeveloped organism requires circulating blood. This need dictates the early appearance of a contractile heart, which is the first functional organ in both the avian and mammalian embryo. The heart arises from paired mesodermal regions within the anterior half of the embryo. As development proceeds, these bilateral precardiac fields merge at the midline to give rise to the primary heart tube. How specific areas of nondifferentiated mesoderm organize into myocardial tissue has been a question that has long intrigued developmental biologists. In recent years, the regulation of Wnt signal transduction has been implicated as an important event that initiates cardiac development. While initial reports in Drosophila and the bird had implicated Wnt proteins as promoters of cardiac tissue formation, subsequent findings that the WNT inhibitors Dkk1 and crescent possess cardiac-inducing activities led to the contrary hypothesis that WNTs actively inhibit cardiogenesis. This seeming contradiction has been resolved, in part, by more recent information indicating that Wnts stimulate multiple signal transduction pathways. In this review, we will examine what is presently known about the importance of regulated Wnt activity for the formation of the heart and the development of the myocardium and discuss this information in context of the emerging complexity of Wnt signal transduction.     

Sensory transduction to the flagellar motor of Sinorhizobium meliloti

Molecular mechanisms that govern chemotaxis and motility in the nitrogen-fixing soil bacterium, Sinorhizobium meliloti, are distinguished from the well-studied taxis systems of enterobacteria by new features. (i) In addition to six transmembrane chemotaxis receptors, S. meliloti has two cytoplasmic receptor proteins, McpY (methyl-accepting chemotaxis protein) and IcpA (internal chemotaxis protein). (ii) The tactic response is mediated by two response regulators, CheY1 and CheY2, but no phosphatase, CheZ. Phosphorylated CheY2 (CheY2-P) is the main regulator of motor function, whereas CheY1 assumes the role of a 'sink' for phosphate that is shuttled from CheY2-P back to CheA. This phospho-transfer from surplus CheY2-P to CheA to CheY1 replaces CheZ phosphatase. (iii) S. meliloti flagella have a complex structure with three helical ribbons that render the filaments rigid and unable to undergo polymorphic transitions from right- to left-handedness. Flagella rotate only clockwise and their motors can increase and decrease rotary speed. Hence, directional changes of a swimming cell occur during slow-down, when several flagella rotate at different speed. Two novel motility proteins, the periplasmic MotC and the cytoplasmic MotD, are essential for motility and rotary speed variation. A model consistent with these data postulates a MotC-mediated gating of the energizing MotA-MotB proton channels leading to variations in flagellar rotary speed.     

Sensory transduction: the 'swarm intelligence' of auditory hair bundles

In vertebrate hair cells, the hair bundle is responsible for the conversion of mechanical vibrations into electrical signals. In a combined experimental and computational tour de force, a group of researchers now presents a quantitative model that explains how the bundle's specific microarchitecture gives rise to its exquisite mechanosensory properties.     

PKC-epsilon is upstream and PKC-alpha is downstream of mitoKATP channels in the signal transduction pathway of ischemic preconditioning of human myocardium

Protein kinase C (PKC) is involved in the process of ischemic preconditioning (IPC), although the precise mechanism is still a subject of debate. Using specific PKC inhibitors, we investigated which PKC isoforms were involved in IPC of the human atrial myocardium sections and to determine their temporal relationship to the opening of mitochondrial potassium-sensitive ATP (mitoK_ATP) channels. Right atrial muscles obtained from patients undergoing elective cardiac surgery were equilibrated and then randomized to receive any of the following protocols: aerobic control, 90-min simulated ischemia/120-min reoxygenation, IPC using 5-min simulated ischemia/5-min reoxygenation followed by 90-min simulated ischemia/120-min reoxygenation and finally, PKC inhibitors were added 10 min before and 10 min during IPC followed by 90-min simulated ischemia/120-min reoxygenation. The PKC isoforms inhibitors investigated were V1–2 peptide, GO-6976, rottlerin, and LY-333531 for PKC-, -, - and -, respectively. To investigate the relation of PKC isoforms to mitoK_ATP channels, PKC inhibitors found to be involved in IPC were added 10 min before and 10 min during preconditioning by diazoxide followed by 90-min simulated ischemia/120-min reoxygenation in a second experiment. Creatine kinase leakage and methylthiazoletetrazolium cell viability were measured. Phosphorylation of PKC isoforms after activation of the sample by either diazoxide or IPC was detected by using Western blot analysis and then analyzed by using Scion image software. PKC- and - inhibitors blocked IPC, whereas PKC- and - inhibitors did not. The protection elicited by diazoxide, believed to be via mitoK_ATP channels opening, was blocked by the inhibition of PKC- but not - isoforms. In addition, diazoxide caused increased phosphorylation of PKC- to the same extent as IPC but did not affect the phosphorylation of PKC-, a process believed to be critical in PKC activation. The results demonstrate that PKC- and - are involved in IPC of the human myocardium with PKC- being upstream and PKC- being downstream of mitoK_ATP channels. cardioprotection; protein kinase C isoforms     

Sensory transduction and electrical signaling in guard cells

Guard cells are a valuable model system for the study of photoreception, ion transport, and osmoregulation in plant cells. Changes in stomatal apertures occur when sensing mechanisms within the guard cells transduce environmental stimull into the ion fluxes and biosynthesis of organic solutes that regulate turgor. The electrical events mediating sensory transduction in guard cells can be characterized with a variety of electrophysiological recording techniques. Recent experiments applying the patch clamp method to guard cell protoplasts have demonstrated activation of electrogenic pumps by blue and red light as well as the presence of potassium channels in guard cell plasmalemma. Light activation of electrogenic proton pumping and the ensuing gating of voltage-dependent ion channels appear to be components of sensory transduction of the stomatal response to light. Mechanisms underlying stomatal control by environmental signals can be understood by studying electrical events associated with ion transport.     

Protective effect of lithium oxybutyrate on the ischemic myocardium

In the experiments on different animal species (mice, cats, dogs) lithium hydroxybutyrate has been shown to have antihypoxic and anti-ischemic effects. Lithium hydroxybutyrate improved the functional state of the ischemic myocardium, stimulated the accumulation of macroergic phosphates (ATP) in the heart, protected the ischemic myocardium and delayed the progression of the reversible ischemic damage into the irreversible one. The improvement of the collateral coronary circulation plays an important role in the anti-ischemic action of the drug.     

Sensory transduction, the gateway to perception: mechanisms and pathology

The 102nd biannual Boehringer Ingelheim Fonds International Titisee Conference took place in October 2010. In the welcoming atmosphere of the small lakeside resort in the Black Forest, southern Germany, scientists from around the world gathered to discuss current topics and challenges in the area of sensory biology. The research presented covered all of the classical Aristotelian senses (and beyond) and provided a glimpse at recent progress and recurring themes in the sensory systems.     

Formation of products of anaerobic metabolism in the ischemic myocardium

The effect of ischemia on the formation of products of anaerobic metabolism and their release into the cardiac effluent in isolated perfused guinea pig hearts was studied. During 30 min normothermal ischemia, the myocardial ATP and phosphocreatine levels decreased to 34% and 15% of the initial values, respectively. The net alanine formation in ischemia was approximately a stoichiometric glutamate decrease; the increase in the tissue malate content corresponded to the aspartate----oxaloacetate----malate anaplerotic flux, the succinate production being commensurable to alpha-ketoglutaric acid formation in the alanine aminotransferase reaction. Using 1H-NMR, it was shown that the release of trace amounts of lactate, alanine, succinate, creatine and pyruvate into cardiac effluents occurred during the first 5 minutes of reperfusion. The rate of metabolite release decreased in the following order: lactate much greater than alanine greater than succinate greater than creatine. By the 30th minute of reperfusion, the decrease in the tissue levels of these metabolites to preischemic values was accompanied by the recovery of ATP and phosphocreatine to 65% and 90% of the initial levels, respectively. The data obtained suggest that the formation and release of alanine, creatine or succinate as well as lactate from ischemic myocardium may testify to significant disturbances in energy metabolism of the myocardium.