Role of the Cellular Stress Response in the Biogenesis of Cysteamine‐Induced Astrocytic Inclusions in Primary Culture

— Cysteamine (CSH; 2‐mercaptoethylamine) stimulates the accumulation of peroxidase‐positive inclusions in cultured astroglia akin to those observed in the aging periventricular brain. Because CSH induces the synthesis of a stress protein (heme oxygenase) in rat liver, we hypothesized that aspects of...

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Veröffentlicht in:Journal of neurochemistry 1993-11, Vol.61 (5), p.1755-1765
Hauptverfasser: Mydlarski, Marc B., Liang, Jin‐Jun, Schipper, Hyman M.
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container_issue 5
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container_title Journal of neurochemistry
container_volume 61
creator Mydlarski, Marc B.
Liang, Jin‐Jun
Schipper, Hyman M.
description — Cysteamine (CSH; 2‐mercaptoethylamine) stimulates the accumulation of peroxidase‐positive inclusions in cultured astroglia akin to those observed in the aging periventricular brain. Because CSH induces the synthesis of a stress protein (heme oxygenase) in rat liver, we hypothesized that aspects of the cellular stress response may play a role in the biogenesis of CSH‐induced astro‐cyte granules. In the present study, we performed indirect immunofluorescent staining and immunoblotting for various stress proteins in rat neuroglial cultures. Exposure of astrocyte cultures to CSH enhanced immunostaining for heme oxygenase‐1 (HO‐1) and heat‐shock proteins 27, 72, and 90, but not glucose‐regulated protein 94, relative to untreated cultures. CSH‐pretreated astrocytes exhibited enhanced tolerance to H2O2 toxicity relative to untreated cells, providing physiological evidence of an antecedent stress response in the former. In addition, exposure for 12 days to H2O2, a known inducer of the stress response, elicited astrocyte granulation similar to that observed with CSH. Chronic induction of HO‐1 and other stress proteins may participate in the biogenesis of metal‐loporphyrin‐rich inclusions in CSH‐treated astroglial cultures and in astrocytes of the aging periventricular brain.
doi_str_mv 10.1111/j.1471-4159.1993.tb09813.x
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Because CSH induces the synthesis of a stress protein (heme oxygenase) in rat liver, we hypothesized that aspects of the cellular stress response may play a role in the biogenesis of CSH‐induced astro‐cyte granules. In the present study, we performed indirect immunofluorescent staining and immunoblotting for various stress proteins in rat neuroglial cultures. Exposure of astrocyte cultures to CSH enhanced immunostaining for heme oxygenase‐1 (HO‐1) and heat‐shock proteins 27, 72, and 90, but not glucose‐regulated protein 94, relative to untreated cultures. CSH‐pretreated astrocytes exhibited enhanced tolerance to H2O2 toxicity relative to untreated cells, providing physiological evidence of an antecedent stress response in the former. In addition, exposure for 12 days to H2O2, a known inducer of the stress response, elicited astrocyte granulation similar to that observed with CSH. 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Psychology ; Heat-Shock Proteins - biosynthesis ; Heat-Shock Proteins - isolation &amp; purification ; Heme Oxygenase (Decyclizing) - biosynthesis ; Hydrogen Peroxide - pharmacology ; Inclusion Bodies - drug effects ; Inclusion Bodies - ultrastructure ; Isolated neuron and nerve. 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Because CSH induces the synthesis of a stress protein (heme oxygenase) in rat liver, we hypothesized that aspects of the cellular stress response may play a role in the biogenesis of CSH‐induced astro‐cyte granules. In the present study, we performed indirect immunofluorescent staining and immunoblotting for various stress proteins in rat neuroglial cultures. Exposure of astrocyte cultures to CSH enhanced immunostaining for heme oxygenase‐1 (HO‐1) and heat‐shock proteins 27, 72, and 90, but not glucose‐regulated protein 94, relative to untreated cultures. CSH‐pretreated astrocytes exhibited enhanced tolerance to H2O2 toxicity relative to untreated cells, providing physiological evidence of an antecedent stress response in the former. In addition, exposure for 12 days to H2O2, a known inducer of the stress response, elicited astrocyte granulation similar to that observed with CSH. Chronic induction of HO‐1 and other stress proteins may participate in the biogenesis of metal‐loporphyrin‐rich inclusions in CSH‐treated astroglial cultures and in astrocytes of the aging periventricular brain.</description><subject>Animals</subject><subject>Animals, Newborn</subject><subject>Astrocyt</subject><subject>Astrocytes - drug effects</subject><subject>Astrocytes - metabolism</subject><subject>Astrocytes - ultrastructure</subject><subject>Biological and medical sciences</subject><subject>Cell Survival - drug effects</subject><subject>Cells, Cultured</subject><subject>Cysteamine - pharmacology</subject><subject>Dose-Response Relationship, Drug</subject><subject>eat‐shock protein</subject><subject>Electrophoresis, Polyacrylamide Gel</subject><subject>eme oxygenase</subject><subject>eroxidase activity</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Heat-Shock Proteins - biosynthesis</subject><subject>Heat-Shock Proteins - isolation &amp; purification</subject><subject>Heme Oxygenase (Decyclizing) - biosynthesis</subject><subject>Hydrogen Peroxide - pharmacology</subject><subject>Inclusion Bodies - drug effects</subject><subject>Inclusion Bodies - ultrastructure</subject><subject>Isolated neuron and nerve. Neuroglia</subject><subject>Kinetics</subject><subject>lucose‐regulated protei</subject><subject>Molecular Weight</subject><subject>Nerve Tissue Proteins - biosynthesis</subject><subject>Nerve Tissue Proteins - isolation &amp; purification</subject><subject>Neuroglia - cytology</subject><subject>Neuroglia - drug effects</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Vertebrates: nervous system and sense organs</subject><subject>ysteamin</subject><issn>0022-3042</issn><issn>1471-4159</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1993</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqVkM9u1DAQxi1EVZbCIyBFCHFL6rGTOOaCSkRhqwpQgbPlOBPwKptsPYnavfEIPGOfhKQb7Z25zOH7vvnzY-w18ASmOt8kkCqIU8h0AlrLZKi4LkAm90_Y6ig9ZSvOhYglT8Uz9pxowznkaQ6n7LQQotAaVuzupm8x6pto-I1RiW07tjZE34eARNEN0q7vCCPfPeoffP8LOyRPc6Lc04B26zt8-PN33dWjwzq6oCH0bj94F607147kpwFz_lvwWxv2UTm2wxjwBTtpbEv4culn7Oflxx_l5_j666d1eXEdu1TyLK6zKpWA4FSu09pKLKZPnc7ySiDUgCqtQIOyuaoqJ0VTFNhgI3kluAaQTp6xt4e5u9DfjkiD2Xpy05-2w34kA7nKlRIwGd8djC70RAEbsztcbICbmbrZmBmtmdGambpZqJv7Kfxq2TJWW6yP0QXzpL9ZdEvOtk2wnfN0tEmlizxVk-39wXbnW9z_xwHm6ksJKsvkP-jIoZ0</recordid><startdate>199311</startdate><enddate>199311</enddate><creator>Mydlarski, Marc B.</creator><creator>Liang, Jin‐Jun</creator><creator>Schipper, Hyman M.</creator><general>Blackwell Publishing Ltd</general><general>Blackwell</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope></search><sort><creationdate>199311</creationdate><title>Role of the Cellular Stress Response in the Biogenesis of Cysteamine‐Induced Astrocytic Inclusions in Primary Culture</title><author>Mydlarski, Marc B. ; Liang, Jin‐Jun ; Schipper, Hyman M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4305-d5b431e1c7694da3e8b09c956b2e1d1e74b1917a67bbc32f88efef30b209113c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1993</creationdate><topic>Animals</topic><topic>Animals, Newborn</topic><topic>Astrocyt</topic><topic>Astrocytes - drug effects</topic><topic>Astrocytes - metabolism</topic><topic>Astrocytes - ultrastructure</topic><topic>Biological and medical sciences</topic><topic>Cell Survival - drug effects</topic><topic>Cells, Cultured</topic><topic>Cysteamine - pharmacology</topic><topic>Dose-Response Relationship, Drug</topic><topic>eat‐shock protein</topic><topic>Electrophoresis, Polyacrylamide Gel</topic><topic>eme oxygenase</topic><topic>eroxidase activity</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Heat-Shock Proteins - biosynthesis</topic><topic>Heat-Shock Proteins - isolation &amp; purification</topic><topic>Heme Oxygenase (Decyclizing) - biosynthesis</topic><topic>Hydrogen Peroxide - pharmacology</topic><topic>Inclusion Bodies - drug effects</topic><topic>Inclusion Bodies - ultrastructure</topic><topic>Isolated neuron and nerve. Neuroglia</topic><topic>Kinetics</topic><topic>lucose‐regulated protei</topic><topic>Molecular Weight</topic><topic>Nerve Tissue Proteins - biosynthesis</topic><topic>Nerve Tissue Proteins - isolation &amp; purification</topic><topic>Neuroglia - cytology</topic><topic>Neuroglia - drug effects</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Vertebrates: nervous system and sense organs</topic><topic>ysteamin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mydlarski, Marc B.</creatorcontrib><creatorcontrib>Liang, Jin‐Jun</creatorcontrib><creatorcontrib>Schipper, Hyman M.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><jtitle>Journal of neurochemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mydlarski, Marc B.</au><au>Liang, Jin‐Jun</au><au>Schipper, Hyman M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Role of the Cellular Stress Response in the Biogenesis of Cysteamine‐Induced Astrocytic Inclusions in Primary Culture</atitle><jtitle>Journal of neurochemistry</jtitle><addtitle>J Neurochem</addtitle><date>1993-11</date><risdate>1993</risdate><volume>61</volume><issue>5</issue><spage>1755</spage><epage>1765</epage><pages>1755-1765</pages><issn>0022-3042</issn><eissn>1471-4159</eissn><coden>JONRA9</coden><abstract>— Cysteamine (CSH; 2‐mercaptoethylamine) stimulates the accumulation of peroxidase‐positive inclusions in cultured astroglia akin to those observed in the aging periventricular brain. Because CSH induces the synthesis of a stress protein (heme oxygenase) in rat liver, we hypothesized that aspects of the cellular stress response may play a role in the biogenesis of CSH‐induced astro‐cyte granules. In the present study, we performed indirect immunofluorescent staining and immunoblotting for various stress proteins in rat neuroglial cultures. Exposure of astrocyte cultures to CSH enhanced immunostaining for heme oxygenase‐1 (HO‐1) and heat‐shock proteins 27, 72, and 90, but not glucose‐regulated protein 94, relative to untreated cultures. CSH‐pretreated astrocytes exhibited enhanced tolerance to H2O2 toxicity relative to untreated cells, providing physiological evidence of an antecedent stress response in the former. In addition, exposure for 12 days to H2O2, a known inducer of the stress response, elicited astrocyte granulation similar to that observed with CSH. 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subjects Animals
Animals, Newborn
Astrocyt
Astrocytes - drug effects
Astrocytes - metabolism
Astrocytes - ultrastructure
Biological and medical sciences
Cell Survival - drug effects
Cells, Cultured
Cysteamine - pharmacology
Dose-Response Relationship, Drug
eat‐shock protein
Electrophoresis, Polyacrylamide Gel
eme oxygenase
eroxidase activity
Fundamental and applied biological sciences. Psychology
Heat-Shock Proteins - biosynthesis
Heat-Shock Proteins - isolation & purification
Heme Oxygenase (Decyclizing) - biosynthesis
Hydrogen Peroxide - pharmacology
Inclusion Bodies - drug effects
Inclusion Bodies - ultrastructure
Isolated neuron and nerve. Neuroglia
Kinetics
lucose‐regulated protei
Molecular Weight
Nerve Tissue Proteins - biosynthesis
Nerve Tissue Proteins - isolation & purification
Neuroglia - cytology
Neuroglia - drug effects
Rats
Rats, Sprague-Dawley
Vertebrates: nervous system and sense organs
ysteamin
title Role of the Cellular Stress Response in the Biogenesis of Cysteamine‐Induced Astrocytic Inclusions in Primary Culture
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