ABSTRACT
Hypoxic exposure of cells or organisms induces expression of a number of hypoxia responsive genes through the activation of the hypoxia-inducible factor-1 (HIF-1). One of the most prominent HIF-1 targets is erythropoietin that has beneficial effects on ischemia-related injury in the brain. Exposure to low environmental oxygen concentrations can be used as a preconditioning paradigm to protect cells or tissues against a variety of harmful conditions. Here, we summarize recent work on neuroprotection of retinal photoreceptors and ganglion cells induced by hypoxic preconditioning or by systemically elevated levels of Epo in mouse plasma.
Subject(s)
Erythropoietin/physiology , Hypoxia/metabolism , Retinal Degeneration/metabolism , Retinal Degeneration/prevention & control , Animals , Erythropoietin/biosynthesis , Erythropoietin/genetics , Humans , Hypoxia/pathology , Hypoxia/physiopathology , Retinal Degeneration/pathology , Retinal Ganglion Cells/metabolism , Retinal Ganglion Cells/pathologyABSTRACT
Oxidative stress has been implicated in mechanisms leading to neuronal cell injury in various pathological states of the brain. Here, we investigated the effect of peroxide exposure on the expression of genes coding for cytoplasmic and endoplasmic reticulum (ER) stress proteins. Primary neuronal cell cultures were exposed to H(2)O(2) for 6 h and mRNA levels of hsp70, grp78, grp94, gadd153 were evaluated by quantitative PCR. In addition, peroxide-induced changes in protein synthesis and cell viability were investigated. Peroxide treatment of cells triggered an almost 12-fold increase in hsp70 mRNA levels, but a significant decrease in grp78, grp94 and gadd153 mRNA levels. To establish whether peroxide exposure blocks the ER-resident stress response, cells were also exposed to thapsigargin (Tg, a specific inhibitor of ER Ca(2+)-ATPase) which has been shown to elicit the ER stress response. Tg exposure induced 7.2-fold, 3.6-fold and 8.8-fold increase in grp78, grp94 and gadd153 mRNA levels, respectively. However, after peroxide pre-exposure, the Tg-induced effect on grp78, grp94 and gadd153 mRNA levels was completely blocked. The results indicate that oxidative damage causes a selective down-regulation of the neuronal stress response activated under conditions of ER dysfunction. This down-regulation was only observed in cultures exposed to peroxide levels which induced severe suppression of protein synthesis and cell injury, implying a causative link between peroxide-induced down-regulation of ER stress response system and development of neuronal cell injury. These observations could have implications for our understanding of the mechanisms underlying neuronal cell injury in pathological states of the brain associated with oxidative damage, including Alzheimer's disease where the neuronal stress response activated under conditions of ER dysfunction has been shown to be down-regulated. Down-regulation of ER stress response may increase the sensitivity of neurones to an otherwise nonlethal form of stress.
Subject(s)
Brain/physiology , Endoplasmic Reticulum/physiology , Gene Expression Regulation/drug effects , Heat-Shock Proteins/genetics , Hydrogen Peroxide/pharmacology , Neurons/physiology , Oxidative Stress/physiology , Transcription, Genetic/drug effects , Animals , Brain/cytology , CCAAT-Enhancer-Binding Proteins/genetics , Carrier Proteins/genetics , Cells, Cultured , Embryo, Mammalian , Endoplasmic Reticulum/drug effects , Endoplasmic Reticulum Chaperone BiP , HSP70 Heat-Shock Proteins/genetics , Kinetics , Membrane Proteins/genetics , Molecular Chaperones/genetics , Nerve Tissue Proteins/genetics , Neurons/cytology , Neurons/drug effects , Polymerase Chain Reaction , RNA, Messenger/genetics , Rats , Rats, Wistar , Transcription Factor CHOP , Transcription Factors/geneticsABSTRACT
Large quantities of medical resources are necessary for the treatment of patients suffering from acute radiation syndrome in combination with blast and thermal injuries (combined injuries). So far, however, there is no tool available for evaluating the resources required for the treatment of combined injuries. The purpose of this manuscript is to describe the scientific basis for a newly developed software tool designed to estimate the medical resources needed for treating the combined injuries of individuals/high numbers of casualties who may be involved in civil defense, emergency medical care and various military activities (namely out of area) in the case of a nuclear event.
Subject(s)
Disaster Planning/statistics & numerical data , Health Resources/supply & distribution , Mathematical Computing , Nuclear Warfare , Radioactive Hazard Release/statistics & numerical data , Blast Injuries/epidemiology , Burns/epidemiology , Dose-Response Relationship, Radiation , Humans , Radiation Injuries/epidemiology , Software DesignABSTRACT
The influence of stirrer speed in the third preculture on the performance of penicillin V production by Penicillium chrysogenum in complex medium in a 100-l air-lift tower loop reactor was investigated. The process performance in the main culture was improved by increasing the stirrer speed from 500 to 750 rpm: the pellet size was reduced to half, the cell growth was influenced only slightly, but the production phase was extended considerably, and the final penicillin concentration was increased from 5.1 g l-1 to 10.4 g l-1.
