Platinum drugs and neurotoxicity: effects on intracellular calcium homeostasis
[Pt( O , O ′-acac)(γ-acac)(DMS)] (PtAcacDMS) is a new platinum compound showing low reactivity with nucleobases and specific reactivity with sulfur ligands intracellularly. It induces apoptosis in breast cancer cells, but appears to be less neurotoxic to the developing cerebellum than cisplatin (cis...
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| Veröffentlicht in: | Cell biology and toxicology 2013-10, Vol.29 (5), p.339-353 |
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| creator | Piccolini, Valeria Maria Bottone, Maria Grazia Bottiroli, Giovanni De Pascali, Sandra Angelica Fanizzi, Francesco Paolo Bernocchi, Graziella |
| description | [Pt(
O
,
O
′-acac)(γ-acac)(DMS)] (PtAcacDMS) is a new platinum compound showing low reactivity with nucleobases and specific reactivity with sulfur ligands intracellularly. It induces apoptosis in breast cancer cells, but appears to be less neurotoxic to the developing cerebellum than cisplatin (cisPt). The aim of this study was to assess the neurotoxicity of platinum compounds on calcium homeostasis in the dentate gyrus and Cornu Ammonis regions of the hippocampal formation during rat postnatal development. Two intracellular calcium homeostasis systems were taken for measurement, calbindin, a calcium buffer protein, and a plasma membrane calcium ATPase (PMCA1). The platinum compounds showed different effects on these markers in the two areas. One day after injection (PD11), cisPt decreased calbindin immunoreactivity and PMCA1 labeling in both regions; at PD17, the downregulation of PMCA1 persisted. Instead, PtAcacDMS produced varying effects on calbindin immunoreactivity in the two regions at PD11 and PD17; but in all cases, the changes incurred in calbindin immunoreactivity were counterbalanced by changes produced in PMCA1 expression. In conclusion, PtAcacDMS seems to affect calcium homeostasis in the central nervous system differently than cisPt. Both the platinum compounds act early to alter the calbindin buffering system. However, the most important difference between cisPt and PtAcacDMS is that, in vivo, the latter acts early to stimulate calcium efflux from nerve cells as reflected by its effect on PMCA1. The rapid onset of an activated calcium pump appears to be essential to cope with the excessive intracellular calcium concentration stemming from the downregulation of calbindin which could damage neuron function and morphology. |
| doi_str_mv | 10.1007/s10565-013-9252-3 |
| format | Article |
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O
,
O
′-acac)(γ-acac)(DMS)] (PtAcacDMS) is a new platinum compound showing low reactivity with nucleobases and specific reactivity with sulfur ligands intracellularly. It induces apoptosis in breast cancer cells, but appears to be less neurotoxic to the developing cerebellum than cisplatin (cisPt). The aim of this study was to assess the neurotoxicity of platinum compounds on calcium homeostasis in the dentate gyrus and Cornu Ammonis regions of the hippocampal formation during rat postnatal development. Two intracellular calcium homeostasis systems were taken for measurement, calbindin, a calcium buffer protein, and a plasma membrane calcium ATPase (PMCA1). The platinum compounds showed different effects on these markers in the two areas. One day after injection (PD11), cisPt decreased calbindin immunoreactivity and PMCA1 labeling in both regions; at PD17, the downregulation of PMCA1 persisted. Instead, PtAcacDMS produced varying effects on calbindin immunoreactivity in the two regions at PD11 and PD17; but in all cases, the changes incurred in calbindin immunoreactivity were counterbalanced by changes produced in PMCA1 expression. In conclusion, PtAcacDMS seems to affect calcium homeostasis in the central nervous system differently than cisPt. Both the platinum compounds act early to alter the calbindin buffering system. However, the most important difference between cisPt and PtAcacDMS is that, in vivo, the latter acts early to stimulate calcium efflux from nerve cells as reflected by its effect on PMCA1. The rapid onset of an activated calcium pump appears to be essential to cope with the excessive intracellular calcium concentration stemming from the downregulation of calbindin which could damage neuron function and morphology.</description><identifier>ISSN: 0742-2091</identifier><identifier>EISSN: 1573-6822</identifier><identifier>DOI: 10.1007/s10565-013-9252-3</identifier><identifier>PMID: 23982140</identifier><language>eng</language><publisher>Dordrecht: Springer Netherlands</publisher><subject>Animals ; Antineoplastic Agents - toxicity ; Apoptosis ; Biochemistry ; Biomedical and Life Sciences ; CA2 Region, Hippocampal - drug effects ; CA2 Region, Hippocampal - growth & development ; CA2 Region, Hippocampal - metabolism ; CA2 Region, Hippocampal - pathology ; CA3 Region, Hippocampal - drug effects ; CA3 Region, Hippocampal - growth & development ; CA3 Region, Hippocampal - metabolism ; CA3 Region, Hippocampal - pathology ; Calbindin 1 - metabolism ; Calcium ; Calcium - metabolism ; Cell Biology ; Central nervous system ; Cisplatin - toxicity ; Dentate Gyrus - drug effects ; Dentate Gyrus - growth & development ; Dentate Gyrus - metabolism ; Dentate Gyrus - pathology ; Developmental biology ; Homeostasis ; Homeostasis - drug effects ; Immunohistochemistry ; Life Sciences ; Neurotoxicity ; Organoplatinum Compounds - toxicity ; Original Research ; Pharmacology ; Pharmacology/Toxicology ; Plasma Membrane Calcium-Transporting ATPases - metabolism ; Platinum ; Rats ; Rats, Wistar ; Sulfur</subject><ispartof>Cell biology and toxicology, 2013-10, Vol.29 (5), p.339-353</ispartof><rights>Springer Science+Business Media Dordrecht 2013</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c405t-329fd1963ffdc0efc6f5f462152d72c53189c8afd49a73ff370625b43756502c3</citedby><cites>FETCH-LOGICAL-c405t-329fd1963ffdc0efc6f5f462152d72c53189c8afd49a73ff370625b43756502c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10565-013-9252-3$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10565-013-9252-3$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23982140$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Piccolini, Valeria Maria</creatorcontrib><creatorcontrib>Bottone, Maria Grazia</creatorcontrib><creatorcontrib>Bottiroli, Giovanni</creatorcontrib><creatorcontrib>De Pascali, Sandra Angelica</creatorcontrib><creatorcontrib>Fanizzi, Francesco Paolo</creatorcontrib><creatorcontrib>Bernocchi, Graziella</creatorcontrib><title>Platinum drugs and neurotoxicity: effects on intracellular calcium homeostasis</title><title>Cell biology and toxicology</title><addtitle>Cell Biol Toxicol</addtitle><addtitle>Cell Biol Toxicol</addtitle><description>[Pt(
O
,
O
′-acac)(γ-acac)(DMS)] (PtAcacDMS) is a new platinum compound showing low reactivity with nucleobases and specific reactivity with sulfur ligands intracellularly. It induces apoptosis in breast cancer cells, but appears to be less neurotoxic to the developing cerebellum than cisplatin (cisPt). The aim of this study was to assess the neurotoxicity of platinum compounds on calcium homeostasis in the dentate gyrus and Cornu Ammonis regions of the hippocampal formation during rat postnatal development. Two intracellular calcium homeostasis systems were taken for measurement, calbindin, a calcium buffer protein, and a plasma membrane calcium ATPase (PMCA1). The platinum compounds showed different effects on these markers in the two areas. One day after injection (PD11), cisPt decreased calbindin immunoreactivity and PMCA1 labeling in both regions; at PD17, the downregulation of PMCA1 persisted. Instead, PtAcacDMS produced varying effects on calbindin immunoreactivity in the two regions at PD11 and PD17; but in all cases, the changes incurred in calbindin immunoreactivity were counterbalanced by changes produced in PMCA1 expression. In conclusion, PtAcacDMS seems to affect calcium homeostasis in the central nervous system differently than cisPt. Both the platinum compounds act early to alter the calbindin buffering system. However, the most important difference between cisPt and PtAcacDMS is that, in vivo, the latter acts early to stimulate calcium efflux from nerve cells as reflected by its effect on PMCA1. The rapid onset of an activated calcium pump appears to be essential to cope with the excessive intracellular calcium concentration stemming from the downregulation of calbindin which could damage neuron function and morphology.</description><subject>Animals</subject><subject>Antineoplastic Agents - toxicity</subject><subject>Apoptosis</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>CA2 Region, Hippocampal - drug effects</subject><subject>CA2 Region, Hippocampal - growth & development</subject><subject>CA2 Region, Hippocampal - metabolism</subject><subject>CA2 Region, Hippocampal - pathology</subject><subject>CA3 Region, Hippocampal - drug effects</subject><subject>CA3 Region, Hippocampal - growth & development</subject><subject>CA3 Region, Hippocampal - metabolism</subject><subject>CA3 Region, Hippocampal - pathology</subject><subject>Calbindin 1 - metabolism</subject><subject>Calcium</subject><subject>Calcium - metabolism</subject><subject>Cell Biology</subject><subject>Central nervous system</subject><subject>Cisplatin - toxicity</subject><subject>Dentate Gyrus - drug effects</subject><subject>Dentate Gyrus - growth & development</subject><subject>Dentate Gyrus - metabolism</subject><subject>Dentate Gyrus - pathology</subject><subject>Developmental biology</subject><subject>Homeostasis</subject><subject>Homeostasis - drug effects</subject><subject>Immunohistochemistry</subject><subject>Life Sciences</subject><subject>Neurotoxicity</subject><subject>Organoplatinum Compounds - toxicity</subject><subject>Original Research</subject><subject>Pharmacology</subject><subject>Pharmacology/Toxicology</subject><subject>Plasma Membrane Calcium-Transporting ATPases - metabolism</subject><subject>Platinum</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Sulfur</subject><issn>0742-2091</issn><issn>1573-6822</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kM1KAzEURoMotlYfwI0MuHEzmuROJjPupPgHRV3oOqSZpKbMTGoyAfv2prSKCK7uIuf77s1B6JTgS4IxvwoEs5LlmEBeU0Zz2ENjwjjkZUXpPhpjXtCc4pqM0FEIS4xxSTg7RCMKdUVJgcfo6aWVg-1jlzU-LkIm-ybrdfRucJ9W2WF9nWljtBpC5vrM9oOXSrdtbKXPlGyVTcl312kXBhlsOEYHRrZBn-zmBL3d3b5OH_LZ8_3j9GaWqwKzIQdam4bUJRjTKKyNKg0zRUkJow2nigGpalVJ0xS15AkCjkvK5gXw9F9MFUzQxbZ35d1H1GEQnQ2bw2SvXQyCFAUkGCqW0PM_6NJF36frEgUcgAKQRJEtpbwLwWsjVt520q8FwWIjW2xliyRbbGQLSJmzXXOcd7r5SXzbTQDdAiE99Qvtf63-t_ULWZSJZQ</recordid><startdate>20131001</startdate><enddate>20131001</enddate><creator>Piccolini, Valeria Maria</creator><creator>Bottone, Maria Grazia</creator><creator>Bottiroli, Giovanni</creator><creator>De Pascali, Sandra Angelica</creator><creator>Fanizzi, Francesco Paolo</creator><creator>Bernocchi, Graziella</creator><general>Springer Netherlands</general><general>Springer Nature B.V</general><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>3V.</scope><scope>7RV</scope><scope>7TK</scope><scope>7TM</scope><scope>7U7</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>P64</scope><scope>PATMY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PYCSY</scope><scope>Q9U</scope><scope>RC3</scope><scope>7QP</scope></search><sort><creationdate>20131001</creationdate><title>Platinum drugs and neurotoxicity: effects on intracellular calcium homeostasis</title><author>Piccolini, Valeria Maria ; Bottone, Maria Grazia ; Bottiroli, Giovanni ; De Pascali, Sandra Angelica ; Fanizzi, Francesco Paolo ; Bernocchi, Graziella</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c405t-329fd1963ffdc0efc6f5f462152d72c53189c8afd49a73ff370625b43756502c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Animals</topic><topic>Antineoplastic Agents - toxicity</topic><topic>Apoptosis</topic><topic>Biochemistry</topic><topic>Biomedical and Life Sciences</topic><topic>CA2 Region, Hippocampal - drug effects</topic><topic>CA2 Region, Hippocampal - growth & development</topic><topic>CA2 Region, Hippocampal - metabolism</topic><topic>CA2 Region, Hippocampal - pathology</topic><topic>CA3 Region, Hippocampal - drug effects</topic><topic>CA3 Region, Hippocampal - growth & development</topic><topic>CA3 Region, Hippocampal - metabolism</topic><topic>CA3 Region, Hippocampal - pathology</topic><topic>Calbindin 1 - metabolism</topic><topic>Calcium</topic><topic>Calcium - metabolism</topic><topic>Cell Biology</topic><topic>Central nervous system</topic><topic>Cisplatin - toxicity</topic><topic>Dentate Gyrus - drug effects</topic><topic>Dentate Gyrus - growth & development</topic><topic>Dentate Gyrus - metabolism</topic><topic>Dentate Gyrus - pathology</topic><topic>Developmental biology</topic><topic>Homeostasis</topic><topic>Homeostasis - drug effects</topic><topic>Immunohistochemistry</topic><topic>Life Sciences</topic><topic>Neurotoxicity</topic><topic>Organoplatinum Compounds - toxicity</topic><topic>Original Research</topic><topic>Pharmacology</topic><topic>Pharmacology/Toxicology</topic><topic>Plasma Membrane Calcium-Transporting ATPases - metabolism</topic><topic>Platinum</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Sulfur</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Piccolini, Valeria Maria</creatorcontrib><creatorcontrib>Bottone, Maria Grazia</creatorcontrib><creatorcontrib>Bottiroli, Giovanni</creatorcontrib><creatorcontrib>De Pascali, Sandra Angelica</creatorcontrib><creatorcontrib>Fanizzi, Francesco Paolo</creatorcontrib><creatorcontrib>Bernocchi, Graziella</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Environmental Science Collection</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>Calcium & Calcified Tissue Abstracts</collection><jtitle>Cell biology and toxicology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Piccolini, Valeria Maria</au><au>Bottone, Maria Grazia</au><au>Bottiroli, Giovanni</au><au>De Pascali, Sandra Angelica</au><au>Fanizzi, Francesco Paolo</au><au>Bernocchi, Graziella</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Platinum drugs and neurotoxicity: effects on intracellular calcium homeostasis</atitle><jtitle>Cell biology and toxicology</jtitle><stitle>Cell Biol Toxicol</stitle><addtitle>Cell Biol Toxicol</addtitle><date>2013-10-01</date><risdate>2013</risdate><volume>29</volume><issue>5</issue><spage>339</spage><epage>353</epage><pages>339-353</pages><issn>0742-2091</issn><eissn>1573-6822</eissn><abstract>[Pt(
O
,
O
′-acac)(γ-acac)(DMS)] (PtAcacDMS) is a new platinum compound showing low reactivity with nucleobases and specific reactivity with sulfur ligands intracellularly. It induces apoptosis in breast cancer cells, but appears to be less neurotoxic to the developing cerebellum than cisplatin (cisPt). The aim of this study was to assess the neurotoxicity of platinum compounds on calcium homeostasis in the dentate gyrus and Cornu Ammonis regions of the hippocampal formation during rat postnatal development. Two intracellular calcium homeostasis systems were taken for measurement, calbindin, a calcium buffer protein, and a plasma membrane calcium ATPase (PMCA1). The platinum compounds showed different effects on these markers in the two areas. One day after injection (PD11), cisPt decreased calbindin immunoreactivity and PMCA1 labeling in both regions; at PD17, the downregulation of PMCA1 persisted. Instead, PtAcacDMS produced varying effects on calbindin immunoreactivity in the two regions at PD11 and PD17; but in all cases, the changes incurred in calbindin immunoreactivity were counterbalanced by changes produced in PMCA1 expression. In conclusion, PtAcacDMS seems to affect calcium homeostasis in the central nervous system differently than cisPt. Both the platinum compounds act early to alter the calbindin buffering system. However, the most important difference between cisPt and PtAcacDMS is that, in vivo, the latter acts early to stimulate calcium efflux from nerve cells as reflected by its effect on PMCA1. The rapid onset of an activated calcium pump appears to be essential to cope with the excessive intracellular calcium concentration stemming from the downregulation of calbindin which could damage neuron function and morphology.</abstract><cop>Dordrecht</cop><pub>Springer Netherlands</pub><pmid>23982140</pmid><doi>10.1007/s10565-013-9252-3</doi><tpages>15</tpages></addata></record> |
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| ispartof | Cell biology and toxicology, 2013-10, Vol.29 (5), p.339-353 |
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| subjects | Animals Antineoplastic Agents - toxicity Apoptosis Biochemistry Biomedical and Life Sciences CA2 Region, Hippocampal - drug effects CA2 Region, Hippocampal - growth & development CA2 Region, Hippocampal - metabolism CA2 Region, Hippocampal - pathology CA3 Region, Hippocampal - drug effects CA3 Region, Hippocampal - growth & development CA3 Region, Hippocampal - metabolism CA3 Region, Hippocampal - pathology Calbindin 1 - metabolism Calcium Calcium - metabolism Cell Biology Central nervous system Cisplatin - toxicity Dentate Gyrus - drug effects Dentate Gyrus - growth & development Dentate Gyrus - metabolism Dentate Gyrus - pathology Developmental biology Homeostasis Homeostasis - drug effects Immunohistochemistry Life Sciences Neurotoxicity Organoplatinum Compounds - toxicity Original Research Pharmacology Pharmacology/Toxicology Plasma Membrane Calcium-Transporting ATPases - metabolism Platinum Rats Rats, Wistar Sulfur |
| title | Platinum drugs and neurotoxicity: effects on intracellular calcium homeostasis |
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