Characterization of the synthesis and accumulation of a 71-kilodalton protein induced in rat tissues after hyperthermia

Currie, R. William; White, Fredric P.

doi:10.1139/o83-059

Cited by 97 publications

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“…P70 and its two isoelectric variants were found predominantly in the soluble fraction (S 3 )' with less in the micro somal fraction (P 3 ) and traces in the p] + P2 frac tion, as previously observed in rat tissues following hyperthermia by Currie and White (1983). P34 was enriched in both particulate fractions.…”

Section: Caudate-putamen and Neocortexsupporting

confidence: 75%

Protein Synthesis in Postischemic Rat Brain: A Two-Dimensional Electrophoretic Analysis

Kiessling

Dienel

Jacewicz

et al. 1986

J Cereb Blood Flow Metab

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Summary: This study examined the pattern of protein synthesis in the neocortex, caudate-putamen, and the hippocampus following transient forebrain ischemia in rats, The animal model of temporary ischemia used in this study causes permanent damage to vulnerable neu rons with a time course of injury that varies fr om hours (caudate nucleus) to days (hippocampus), To examine the spectrum of proteins synthesized in these regions at 3 and 18 h after recirculation, cerebral proteins were pulse-la beled in vivo by an intravenous injection of [ 3 sSJmethio nine. Newly synthesized (3sS-labeled) and constitutive (unlabeled) proteins were analyzed by two-dimensional gel electrophoresis and fluorography, In all three brain regions, specific proteins underwent preferential syn thesis (Mr �27,000, �65,000, �70,000, � I 10,000), while others showed decreased synthesis (neuron-specific eno lase, 0.-and l3-tubulin). There was an early (3 h post isch emia) induction of the Mr � 70,000 mammalian "stress"Tr ansient cerebral ischemia is associated with prolonged severe inhibition of brain protein syn thesis. Gradual recovery occurs long after energy metabolites have been restored and other metabolic processes normalized (Kleihues et aI. , 1975; Cooper et aI., 1977; Dienel et aI., 1980; Nowak et aI., 1985). Although the prolonged impairment of amino acid incorporation does not seem to reduce the total amount of brain protein or the activities of enzymes with low turnover rates, postischemic re- Schlesinger et al. (1982)]. In the present study newly synthesized ( 3 sS-labeled) proteins including stress proteins and constitutive (unlabeled) brain proteins were analyzed by two-dimensional gel electrophoresis and fluorography following the in vivo administration of [ 3 SS]methionine in control and postischemic animals. During transient ischemia (30 min) produced by occlusion of the four major arteries supplying the brain, all forebrain regions are severely ischemic but subsequently differ in the extent and rate of progression of neuronal cell death (Pulsinelli et aI., POSTlSCHEMIC PROTEIN SYNTHESIS IN RAT BRAIN 6431982a,b). Following restoration of cerebral blood flow, ischemic cell death progresses for several hours (in the caudate-putamen) to days (in the hip pocampus and neocortex). The majority of CAl py ramidal neurons and striatal small-to medium-sized neurons die, whereas injury to CA 3 pyramidal or neocortical neurons is relatively mild or absent. This phenomenon of selective and "delayed neu ronal cell death" (Kirino, 1982; Pulsinelli et aI. , 1982a) suggests that neurons remain viable throughout the ischemic period or even hours thereafter, but that certain sUbpopulations subse quently succumb owing to ischemia-induced meta bolic derangements of as-yet unidentified nature. The objective of this investigation was to assess whether regional differences in the spectrum of proteins synthesized by postischemic brain tissue exist and possibly predict the success or failure to recover from a potentially lethal insult. METHODS Ani...

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Section: Caudate-putamen and Neocortexsupporting

confidence: 75%

Protein Synthesis in Postischemic Rat Brain: A Two-Dimensional Electrophoretic Analysis

Kiessling

Dienel

Jacewicz

et al. 1986

J Cereb Blood Flow Metab

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“…Levels of mammalian systems with hyperthermia, it was demonstrated e 2.3-and 3.0-kb HSP70 transcripts were highest in that adrenal glands contained high levels of HSP70 protein in mo ofage. A significant decrease (P < 0.01) in overall the absence of heat stress (41). In that report, the treatment It-induced HSP70 expression was observed when of non-heat-stressed controls was not described in detail.…”

Section: Resultsmentioning

confidence: 77%

Stress-induced heat shock protein 70 expression in adrenal cortex: an adrenocorticotropic hormone-sensitive, age-dependent response.

Blake

Udelsman

Feulner

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

196

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The induction of heat shock proteins (HSP) by cellular stress and the activation of the hypothalamicpituitary-adrenal axis by physiologic stress are biological responses that aid in the maintenance of cellular and organismal homeostasis, respectively. In this report, restraint stress, known to activate the hypothalamic-pituitary-adrenal axis, is shown to induce expression of HSP70 mRNA selectively in the adrenal cortex of the rat. Restraint-induced HSP70 expression in the adrenals is rapid and is preceded by the activation of a protein factor capable of binding to the heat shock transcriptional control element. The ability of restraint to induce HSP70 expression in the adrenal is virtually eliminated in hypophysectomized rats but can be restored by the exogenous administration of adrenocorticotropic hormone. The magnitude of this induction declines as a function of increasing age, which may contribute to a reduced stress tolerance by aged animals. These results support a role for HSP70 in the physiologic stress response mediated by the hypothalamic-pituitary-adrenal axis.The ability of an organism to adapt to stress is a requisite for its survival in an everchanging environment (1). In higher organisms stress results in the activation of the hypothalamic-pituitary-adrenal (HPA) axis. This response is characterized by the secretion ofcorticotropin-releasing hormone from hypothalamic nuclei into the hypophyseal portal system, which, in turn, stimulates the release of adrenocorticotropic hormone (ACTH) from the anterior pituitary into the peripheral circulation. ACTH binds to specific adrenocortical receptors, resulting in the rapid release of glucocorticoids into the bloodstream. Glucocorticoids act on a variety of tissues to give rise to their numerous homeostatic effects (2).At the cellular level, heat and other metabolic stressors induce the synthesis of a set of highly conserved proteins termed heat shock proteins (HSPs) (3). This enhanced gene expression occurs as a result of stress-induced activation of one or more heat shock transcription factors (HSFs) (4-6). These proteins bind to a specific DNA sequence, the heat shock element (HSE) (7-10), in the promotor regions of the HSP genes to increase their rate of transcription. HSPs interact with other cellular proteins under normal and stress conditions and are thought to aid in the maintenance of cellular homeostasis (3).Our current knowledge of HSP function is derived largely from studies in cultured cells. Few investigations have used in vivo stress models that might have direct physiologic relevance. In a previous study we demonstrated that, in response to heat stress, HSP70 is preferentially induced in specific brain regions involved in the regulation of HPA function and hypothesized that HSPs are an integral component of the mammalian physiologic stress response (11). In support of this hypothesis, this report demonstrates that a mild physiologic stress, restraint, induces the expression of the major HSP, HSP70, in rat adrenal cortex. We provide ...

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“…Histogram results are relative to the control group (times mean control values and SE) for each fraction. One-way ANOVA Bonfferoni multicomparison test, confirmed with a nonparametric test, revealed differences in the homogenate, CON vs. HS and HSINS, P ϭ 0.04; cytosolic fraction, CON vs. HS and HSINS, P ϭ 0.02; membrane fraction, CON vs. INS and HSINS, P ϭ 0.03; pellet fraction, CON vs. HSINS, P ϭ 0.03. in rat, but with heat shock or injury, its expression is transiently increased many times (2,15,17). Hsp70 maintains the HSF in an inactivated form in the cell cytoplasm (49,66).…”

Section: Discussionmentioning

confidence: 99%

Insulin induces myocardial protection and Hsp70 localization to plasma membranes in rat hearts

Ali²,

Currie³

2006

American Journal of Physiology-Heart and Circulatory Physiology

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Li, Gefeng, Imtiaz S. Ali, and R. William Currie. Insulin induces myocardial protection and Hsp70 localization to plasma membranes in rat hearts. Am J Physiol Heart Circ Physiol 291: H1709 -H1721, 2006. First published May 26, 2006 doi:10.1152/ajpheart.00201.2006.-Insulin induces the expression of the 70-kDa heat shock protein (Hsp70) in rat hearts. In this study, we examined insulin-and heat shock-treated hearts for improved contractile recovery after 30 min of ischemia, activation of the heat shock transcription factor, and localization of the Hsp70 in relation to dystrophin and ␣-tubulin. Adult male SpragueDawley rats were assigned to groups: 1) control, 2) sham control, 3) insulin injected (200 U/g body wt), 4) heat shock treated (core body temperature 42°C for 15 min), and 5) heat shock and insulin treated. Six hours later, hearts were isolated for Langendorff perfusion to determine cardiac function, or myocardial tissues were collected and prepared for either electrophoretic mobility shift assay, Western blot analysis, or immunofluorescence microscopy. Insulin treatment with 6 h of recovery enhances postischemic myocardial recovery of contractile function and increases Hsp70 expression through activation of the heat shock transcription factor. Insulin-treated hearts had elevated levels of Hsp70, particularly in the membrane fraction. In contrast, heat-shocked hearts had elevated levels of Hsp70 in the cytosol, membrane, and pellet fractions. After insulin treatment, Hsp70 was mostly colocalized to the plasma membrane with dystrophin. In contrast, after heat shock, Hsp70 was localized mostly between cardiomyocytes in apparent vascular or perivascular elements. The localization of Hsp70 is dependent on the inducing stimuli of either heat shock or insulin treatment. The cell membrane versus vascular localization of Hsp70 suggests the interesting possibility of functionally distinct roles for Hsp70 in the heart, whether induced by insulin or heat shock treatment. heat shock; heat shock protein 70; heat shock transcription factor; ischemia/reperfusion INSULIN IS A CRUCIAL REGULATOR of metabolism, and in cardiac muscle, insulin induces glycogen and protein synthesis, and in fat, lipid storage is favored. Insulin also mediates other diverse effects in a wide variety of cells and tissues (57). Sodi-Pallares et al. (67) initially introduced the concept of infusing a metabolic cocktail of glucose, insulin, and potassium to improve recovery from myocardial infarction. Clinical studies (20,22,63) suggest that this cocktail might have an important role in reducing in-hospital mortality after acute cardiac infarction. Initially, two possible mechanisms for the effectiveness of the glucose, insulin, and potassium cocktail were suggested: 1) the promotion of cardiac glycolysis and 2) the uptake of free fatty acids into adipocytes (58). More recently, insulin alone has been shown to be as effective as the glucose, insulin, and potassium cocktail at reducing myocardial ischemia-reperfusion injury (32). The cardioprotective...

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Characterization of the synthesis and accumulation of a 71-kilodalton protein induced in rat tissues after hyperthermia

Cited by 97 publications

References 0 publications

Protein Synthesis in Postischemic Rat Brain: A Two-Dimensional Electrophoretic Analysis

Protein Synthesis in Postischemic Rat Brain: A Two-Dimensional Electrophoretic Analysis

Stress-induced heat shock protein 70 expression in adrenal cortex: an adrenocorticotropic hormone-sensitive, age-dependent response.

Insulin induces myocardial protection and Hsp70 localization to plasma membranes in rat hearts

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