Relationship between cadmium-induced expression of heatshock genes, inhibition of protein synthesis and cell death
Stress proteins (heat shock proteins, HSPs) have been proposed as markers for toxicity. This study has focussed on the pattern of HSP synthesis in relation to cytotoxicity and their dependence on doses of cadmium chloride. We investigated the relationship between cadmium-induced expression of heatsh...
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| Veröffentlicht in: | Toxicology (Amsterdam) 1995-05, Vol.99 (1), p.19-30 |
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| creator | Ovelgönne, J.H. Souren, J.E.M. Wiegant, F.A.C. Van Wijk, R. |
| description | Stress proteins (heat shock proteins, HSPs) have been proposed as markers for toxicity. This study has focussed on the pattern of HSP synthesis in relation to cytotoxicity and their dependence on doses of cadmium chloride. We investigated the relationship between cadmium-induced expression of heatshock genes, inhibition of protein synthesis and cell death in a well-differentiated hepatoma cell line, Reuber H35, under exposure conditions ranging to full (> 98%) lethality. We find a non-linearity in the responses of these cells when the duration of cadmium exposure is varied. The results indicate that sublethal concentrations of cadmium can inhibit protein synthesis and also increase the synthesis of certain HSPs. The pattern of heat shock protein induction changes when exposure conditions become more severe. The most strongly inducible heat shock protein, HSP68, is, surprisingly, only synthesized under conditions which lead to severe inhibition of protein synthesis. The comparison of HSP68 mRNA levels and HSP68 synthesis showed that HSP68 mRNA is already induced under conditions where the synthesis of HSP68 protein cannot yet be traced. From these data we conclude that a differential HSP expression takes place. The translational control of HSP synthesis might be explained by the preferential translation of this mRNA under conditions of severe shut-off of general protein synthesis. |
| doi_str_mv | 10.1016/0300-483X(94)02990-C |
| format | Article |
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This study has focussed on the pattern of HSP synthesis in relation to cytotoxicity and their dependence on doses of cadmium chloride. We investigated the relationship between cadmium-induced expression of heatshock genes, inhibition of protein synthesis and cell death in a well-differentiated hepatoma cell line, Reuber H35, under exposure conditions ranging to full (> 98%) lethality. We find a non-linearity in the responses of these cells when the duration of cadmium exposure is varied. The results indicate that sublethal concentrations of cadmium can inhibit protein synthesis and also increase the synthesis of certain HSPs. The pattern of heat shock protein induction changes when exposure conditions become more severe. The most strongly inducible heat shock protein, HSP68, is, surprisingly, only synthesized under conditions which lead to severe inhibition of protein synthesis. The comparison of HSP68 mRNA levels and HSP68 synthesis showed that HSP68 mRNA is already induced under conditions where the synthesis of HSP68 protein cannot yet be traced. From these data we conclude that a differential HSP expression takes place. The translational control of HSP synthesis might be explained by the preferential translation of this mRNA under conditions of severe shut-off of general protein synthesis.</description><identifier>ISSN: 0300-483X</identifier><identifier>EISSN: 1879-3185</identifier><identifier>DOI: 10.1016/0300-483X(94)02990-C</identifier><identifier>PMID: 7761999</identifier><identifier>CODEN: TXICDD</identifier><language>eng</language><publisher>Shannon: Elsevier Ireland Ltd</publisher><subject>Animals ; Biological and medical sciences ; Blotting, Northern ; Cadmium - pharmacology ; Cadmium Chloride ; Cell Death - drug effects ; Chemical and industrial products toxicology. Toxic occupational diseases ; Chlorides - pharmacology ; Cytotoxicity ; Gene Expression - drug effects ; Heat shock proteins ; Heat shock response ; Heat-Shock Proteins - drug effects ; Heat-Shock Proteins - genetics ; HSP ; Medical sciences ; Metals and various inorganic compounds ; Protein Biosynthesis ; Proteins - drug effects ; Rats ; RNA, Messenger - biosynthesis ; RNA, Messenger - drug effects ; Stress proteins ; Stress response ; Toxicology ; Tumor Cells, Cultured</subject><ispartof>Toxicology (Amsterdam), 1995-05, Vol.99 (1), p.19-30</ispartof><rights>1995</rights><rights>1995 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c417t-29ff44648a135ca0f5c66adf1dbc72c624995aa9a0fa5bf719f7fff7d42f9e1d3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/0300483X9402990C$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=3562113$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/7761999$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ovelgönne, J.H.</creatorcontrib><creatorcontrib>Souren, J.E.M.</creatorcontrib><creatorcontrib>Wiegant, F.A.C.</creatorcontrib><creatorcontrib>Van Wijk, R.</creatorcontrib><title>Relationship between cadmium-induced expression of heatshock genes, inhibition of protein synthesis and cell death</title><title>Toxicology (Amsterdam)</title><addtitle>Toxicology</addtitle><description>Stress proteins (heat shock proteins, HSPs) have been proposed as markers for toxicity. This study has focussed on the pattern of HSP synthesis in relation to cytotoxicity and their dependence on doses of cadmium chloride. We investigated the relationship between cadmium-induced expression of heatshock genes, inhibition of protein synthesis and cell death in a well-differentiated hepatoma cell line, Reuber H35, under exposure conditions ranging to full (> 98%) lethality. We find a non-linearity in the responses of these cells when the duration of cadmium exposure is varied. The results indicate that sublethal concentrations of cadmium can inhibit protein synthesis and also increase the synthesis of certain HSPs. The pattern of heat shock protein induction changes when exposure conditions become more severe. The most strongly inducible heat shock protein, HSP68, is, surprisingly, only synthesized under conditions which lead to severe inhibition of protein synthesis. The comparison of HSP68 mRNA levels and HSP68 synthesis showed that HSP68 mRNA is already induced under conditions where the synthesis of HSP68 protein cannot yet be traced. From these data we conclude that a differential HSP expression takes place. The translational control of HSP synthesis might be explained by the preferential translation of this mRNA under conditions of severe shut-off of general protein synthesis.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Blotting, Northern</subject><subject>Cadmium - pharmacology</subject><subject>Cadmium Chloride</subject><subject>Cell Death - drug effects</subject><subject>Chemical and industrial products toxicology. Toxic occupational diseases</subject><subject>Chlorides - pharmacology</subject><subject>Cytotoxicity</subject><subject>Gene Expression - drug effects</subject><subject>Heat shock proteins</subject><subject>Heat shock response</subject><subject>Heat-Shock Proteins - drug effects</subject><subject>Heat-Shock Proteins - genetics</subject><subject>HSP</subject><subject>Medical sciences</subject><subject>Metals and various inorganic compounds</subject><subject>Protein Biosynthesis</subject><subject>Proteins - drug effects</subject><subject>Rats</subject><subject>RNA, Messenger - biosynthesis</subject><subject>RNA, Messenger - drug effects</subject><subject>Stress proteins</subject><subject>Stress response</subject><subject>Toxicology</subject><subject>Tumor Cells, Cultured</subject><issn>0300-483X</issn><issn>1879-3185</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1995</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE2L1TAUhoMo453Rf6CQhYiC1aRN02YjyGX8gAFBFNyFNDmx0Ta95qTq_HtzveUuXZ3F-7yHl4eQR5y95IzLV6xhrBJ98_WZEs9ZrRSr9nfIjvedqhret3fJ7ozcJ5eI3xljdSPkBbnoOsmVUjuSPsFkclgijuFAB8i_ASK1xs1hnasQ3WrBUfhzSIBYMLp4OoLJOC72B_0GEfAFDXEMQ8hbfEhLhhAp3sY8AgakJjpqYZqoK83xAbnnzYTwcLtX5Mvb68_799XNx3cf9m9uKit4l6taeS-EFL3hTWsN862V0jjP3WC72spaKNUao0pi2sF3XPnOe985UXsF3DVX5Onpbxn0cwXMeg54nGEiLCtqLvuGcd4XUJxAmxbEBF4fUphNutWc6aNqffSojx61Evqfar0vtcfb_3WYwZ1Lm9uSP9lyg9ZMPploA56xppU1503BXp8wKC5-BUgabYBYtIcENmu3hP_v-AuDaZ3B</recordid><startdate>19950505</startdate><enddate>19950505</enddate><creator>Ovelgönne, J.H.</creator><creator>Souren, J.E.M.</creator><creator>Wiegant, F.A.C.</creator><creator>Van Wijk, R.</creator><general>Elsevier Ireland Ltd</general><general>Elsevier Science</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>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>19950505</creationdate><title>Relationship between cadmium-induced expression of heatshock genes, inhibition of protein synthesis and cell death</title><author>Ovelgönne, J.H. ; Souren, J.E.M. ; Wiegant, F.A.C. ; Van Wijk, R.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c417t-29ff44648a135ca0f5c66adf1dbc72c624995aa9a0fa5bf719f7fff7d42f9e1d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1995</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Blotting, Northern</topic><topic>Cadmium - pharmacology</topic><topic>Cadmium Chloride</topic><topic>Cell Death - drug effects</topic><topic>Chemical and industrial products toxicology. Toxic occupational diseases</topic><topic>Chlorides - pharmacology</topic><topic>Cytotoxicity</topic><topic>Gene Expression - drug effects</topic><topic>Heat shock proteins</topic><topic>Heat shock response</topic><topic>Heat-Shock Proteins - drug effects</topic><topic>Heat-Shock Proteins - genetics</topic><topic>HSP</topic><topic>Medical sciences</topic><topic>Metals and various inorganic compounds</topic><topic>Protein Biosynthesis</topic><topic>Proteins - drug effects</topic><topic>Rats</topic><topic>RNA, Messenger - biosynthesis</topic><topic>RNA, Messenger - drug effects</topic><topic>Stress proteins</topic><topic>Stress response</topic><topic>Toxicology</topic><topic>Tumor Cells, Cultured</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ovelgönne, J.H.</creatorcontrib><creatorcontrib>Souren, J.E.M.</creatorcontrib><creatorcontrib>Wiegant, F.A.C.</creatorcontrib><creatorcontrib>Van Wijk, R.</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>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>Toxicology (Amsterdam)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ovelgönne, J.H.</au><au>Souren, J.E.M.</au><au>Wiegant, F.A.C.</au><au>Van Wijk, R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Relationship between cadmium-induced expression of heatshock genes, inhibition of protein synthesis and cell death</atitle><jtitle>Toxicology (Amsterdam)</jtitle><addtitle>Toxicology</addtitle><date>1995-05-05</date><risdate>1995</risdate><volume>99</volume><issue>1</issue><spage>19</spage><epage>30</epage><pages>19-30</pages><issn>0300-483X</issn><eissn>1879-3185</eissn><coden>TXICDD</coden><abstract>Stress proteins (heat shock proteins, HSPs) have been proposed as markers for toxicity. This study has focussed on the pattern of HSP synthesis in relation to cytotoxicity and their dependence on doses of cadmium chloride. We investigated the relationship between cadmium-induced expression of heatshock genes, inhibition of protein synthesis and cell death in a well-differentiated hepatoma cell line, Reuber H35, under exposure conditions ranging to full (> 98%) lethality. We find a non-linearity in the responses of these cells when the duration of cadmium exposure is varied. The results indicate that sublethal concentrations of cadmium can inhibit protein synthesis and also increase the synthesis of certain HSPs. The pattern of heat shock protein induction changes when exposure conditions become more severe. The most strongly inducible heat shock protein, HSP68, is, surprisingly, only synthesized under conditions which lead to severe inhibition of protein synthesis. The comparison of HSP68 mRNA levels and HSP68 synthesis showed that HSP68 mRNA is already induced under conditions where the synthesis of HSP68 protein cannot yet be traced. From these data we conclude that a differential HSP expression takes place. The translational control of HSP synthesis might be explained by the preferential translation of this mRNA under conditions of severe shut-off of general protein synthesis.</abstract><cop>Shannon</cop><cop>Amsterdam</cop><pub>Elsevier Ireland Ltd</pub><pmid>7761999</pmid><doi>10.1016/0300-483X(94)02990-C</doi><tpages>12</tpages></addata></record> |
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| subjects | Animals Biological and medical sciences Blotting, Northern Cadmium - pharmacology Cadmium Chloride Cell Death - drug effects Chemical and industrial products toxicology. Toxic occupational diseases Chlorides - pharmacology Cytotoxicity Gene Expression - drug effects Heat shock proteins Heat shock response Heat-Shock Proteins - drug effects Heat-Shock Proteins - genetics HSP Medical sciences Metals and various inorganic compounds Protein Biosynthesis Proteins - drug effects Rats RNA, Messenger - biosynthesis RNA, Messenger - drug effects Stress proteins Stress response Toxicology Tumor Cells, Cultured |
| title | Relationship between cadmium-induced expression of heatshock genes, inhibition of protein synthesis and cell death |
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