Mechanisms of hydrazine toxicity in rat liver investigated by proteomics and multivariate data analysis
A proteomics approach combined with multivariate data analysis was used to examine the hepatotoxic effect of hydrazine in 30 male Sprague Dawley rats, assigned to four treatment groups and two control groups. Liver samples from the individual animals were resolved by two‐dimensional differential gel...
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| Veröffentlicht in: | Proteomics (Weinheim) 2004-03, Vol.4 (3), p.868-880 |
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| creator | Guldberg Klenø, Tina Rønnedal Leonardsen, Lise Ørsted Kjeldal, Helle Møller Laursen, Steen Nørregaard Jensen, Ole Baunsgaard, Dorrit |
| description | A proteomics approach combined with multivariate data analysis was used to examine the hepatotoxic effect of hydrazine in 30 male Sprague Dawley rats, assigned to four treatment groups and two control groups. Liver samples from the individual animals were resolved by two‐dimensional differential gel electrophoresis (2‐D DIGE) and protein patterns from the 2‐D gels were analyzed by principal component analysis (PCA) and partial least squares regression (PLSR). The PCA plot was able to describe the variation in the protein expression related to dose and time, by separation or clustering of different animal groups. PLSR followed by variable selection (Jack‐knifing) was used to select proteins that varied significantly in relation to the dose related response of the hydrazine treatment. The 10 up‐regulated and 10 down‐regulated proteins with highest rank in the PLSR model were identified by mass spectrometry. Hydrazine treatment induced altered expression of proteins related to lipid metabolism, Ca2+ homeostasis, thyroid hormone pathways and stress response. Several of the identified proteins have not previously been implicated in hydrazine toxicity and may thus be regarded as new potential biomarkers of induced liver toxicity. |
| doi_str_mv | 10.1002/pmic.200300663 |
| format | Article |
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Liver samples from the individual animals were resolved by two‐dimensional differential gel electrophoresis (2‐D DIGE) and protein patterns from the 2‐D gels were analyzed by principal component analysis (PCA) and partial least squares regression (PLSR). The PCA plot was able to describe the variation in the protein expression related to dose and time, by separation or clustering of different animal groups. PLSR followed by variable selection (Jack‐knifing) was used to select proteins that varied significantly in relation to the dose related response of the hydrazine treatment. The 10 up‐regulated and 10 down‐regulated proteins with highest rank in the PLSR model were identified by mass spectrometry. Hydrazine treatment induced altered expression of proteins related to lipid metabolism, Ca2+ homeostasis, thyroid hormone pathways and stress response. Several of the identified proteins have not previously been implicated in hydrazine toxicity and may thus be regarded as new potential biomarkers of induced liver toxicity.</description><identifier>ISSN: 1615-9853</identifier><identifier>EISSN: 1615-9861</identifier><identifier>DOI: 10.1002/pmic.200300663</identifier><identifier>PMID: 14997507</identifier><language>eng</language><publisher>Weinheim: WILEY-VCH Verlag</publisher><subject>Analytical, structural and metabolic biochemistry ; Animals ; Antineoplastic Agents - pharmacology ; Biological and medical sciences ; Biomarkers ; Calcium - metabolism ; Carcinogens ; Chemometrics ; Differential gel electrophoresis ; Dose-Response Relationship, Drug ; Down-Regulation ; Electrophoresis, Gel, Two-Dimensional - methods ; Fundamental and applied biological sciences. Psychology ; Hydrazine toxicity ; Hydrazines - pharmacology ; Hydrazines - toxicity ; Liver - drug effects ; Liver - metabolism ; Male ; Mass Spectrometry ; Miscellaneous ; Multivariate Analysis ; Peptides - chemistry ; Proteins ; Proteins - chemistry ; Proteome ; Proteomics - methods ; Rats ; Rats, Sprague-Dawley ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Time Factors ; Up-Regulation</subject><ispartof>Proteomics (Weinheim), 2004-03, Vol.4 (3), p.868-880</ispartof><rights>Copyright © 2004 WILEY‐VCH Verlag GmbH & Co. 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Liver samples from the individual animals were resolved by two‐dimensional differential gel electrophoresis (2‐D DIGE) and protein patterns from the 2‐D gels were analyzed by principal component analysis (PCA) and partial least squares regression (PLSR). The PCA plot was able to describe the variation in the protein expression related to dose and time, by separation or clustering of different animal groups. PLSR followed by variable selection (Jack‐knifing) was used to select proteins that varied significantly in relation to the dose related response of the hydrazine treatment. The 10 up‐regulated and 10 down‐regulated proteins with highest rank in the PLSR model were identified by mass spectrometry. Hydrazine treatment induced altered expression of proteins related to lipid metabolism, Ca2+ homeostasis, thyroid hormone pathways and stress response. Several of the identified proteins have not previously been implicated in hydrazine toxicity and may thus be regarded as new potential biomarkers of induced liver toxicity.</description><subject>Analytical, structural and metabolic biochemistry</subject><subject>Animals</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Biomarkers</subject><subject>Calcium - metabolism</subject><subject>Carcinogens</subject><subject>Chemometrics</subject><subject>Differential gel electrophoresis</subject><subject>Dose-Response Relationship, Drug</subject><subject>Down-Regulation</subject><subject>Electrophoresis, Gel, Two-Dimensional - methods</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Hydrazine toxicity</subject><subject>Hydrazines - pharmacology</subject><subject>Hydrazines - toxicity</subject><subject>Liver - drug effects</subject><subject>Liver - metabolism</subject><subject>Male</subject><subject>Mass Spectrometry</subject><subject>Miscellaneous</subject><subject>Multivariate Analysis</subject><subject>Peptides - chemistry</subject><subject>Proteins</subject><subject>Proteins - chemistry</subject><subject>Proteome</subject><subject>Proteomics - methods</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization</subject><subject>Time Factors</subject><subject>Up-Regulation</subject><issn>1615-9853</issn><issn>1615-9861</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkMtPGzEQhy1URFLg2mPlS48b_PbusYqaFIkAQq04WrNeb-J2H5FtAtu_vhslCr31NH58v5nRh9AnSmaUEHazbb2dMUI4IUrxMzSlisqsyBX9cDpLPkEfY_xFCNV5oS_QhIqi0JLoKVqvnN1A52MbcV_jzVAF-OM7h1P_5q1PA_YdDpBw43cujJedi8mvIbkKlwPehj65ftwhYugq3L40ye8g-PEfV5BgfIVmiD5eofMamuiuj_US_Vx8-zH_nt09LG_nX-8yK4ngWQ3MSVC65qosVV47KvJSCiGYFbmwoGVRO1HwXLqxSsWlZFXOrCqsYExofolmh7429DEGV5tt8C2EwVBi9sbM3pg5GRsDnw-B7UvZuuodPyoagS9HAKKFpg7QWR_fOSlHq2LfqDhwr75xw3_GmsfV7fzfJbJD1sfk3k5ZCL-N0lxL83y_NKulfn5aMGEW_C-lGJXL</recordid><startdate>200403</startdate><enddate>200403</enddate><creator>Guldberg Klenø, Tina</creator><creator>Rønnedal Leonardsen, Lise</creator><creator>Ørsted Kjeldal, Helle</creator><creator>Møller Laursen, Steen</creator><creator>Nørregaard Jensen, Ole</creator><creator>Baunsgaard, Dorrit</creator><general>WILEY-VCH Verlag</general><general>WILEY‐VCH Verlag</general><general>Wiley-VCH</general><scope>BSCLL</scope><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></search><sort><creationdate>200403</creationdate><title>Mechanisms of hydrazine toxicity in rat liver investigated by proteomics and multivariate data analysis</title><author>Guldberg Klenø, Tina ; Rønnedal Leonardsen, Lise ; Ørsted Kjeldal, Helle ; Møller Laursen, Steen ; Nørregaard Jensen, Ole ; Baunsgaard, Dorrit</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5043-fa2e5a67f36bb68fe148b54442c484ca759fe49385efe4563552d82c69c422473</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Analytical, structural and metabolic biochemistry</topic><topic>Animals</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Biomarkers</topic><topic>Calcium - metabolism</topic><topic>Carcinogens</topic><topic>Chemometrics</topic><topic>Differential gel electrophoresis</topic><topic>Dose-Response Relationship, Drug</topic><topic>Down-Regulation</topic><topic>Electrophoresis, Gel, Two-Dimensional - methods</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Hydrazine toxicity</topic><topic>Hydrazines - pharmacology</topic><topic>Hydrazines - toxicity</topic><topic>Liver - drug effects</topic><topic>Liver - metabolism</topic><topic>Male</topic><topic>Mass Spectrometry</topic><topic>Miscellaneous</topic><topic>Multivariate Analysis</topic><topic>Peptides - chemistry</topic><topic>Proteins</topic><topic>Proteins - chemistry</topic><topic>Proteome</topic><topic>Proteomics - methods</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization</topic><topic>Time Factors</topic><topic>Up-Regulation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Guldberg Klenø, Tina</creatorcontrib><creatorcontrib>Rønnedal Leonardsen, Lise</creatorcontrib><creatorcontrib>Ørsted Kjeldal, Helle</creatorcontrib><creatorcontrib>Møller Laursen, Steen</creatorcontrib><creatorcontrib>Nørregaard Jensen, Ole</creatorcontrib><creatorcontrib>Baunsgaard, Dorrit</creatorcontrib><collection>Istex</collection><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><jtitle>Proteomics (Weinheim)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Guldberg Klenø, Tina</au><au>Rønnedal Leonardsen, Lise</au><au>Ørsted Kjeldal, Helle</au><au>Møller Laursen, Steen</au><au>Nørregaard Jensen, Ole</au><au>Baunsgaard, Dorrit</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mechanisms of hydrazine toxicity in rat liver investigated by proteomics and multivariate data analysis</atitle><jtitle>Proteomics (Weinheim)</jtitle><addtitle>Proteomics</addtitle><date>2004-03</date><risdate>2004</risdate><volume>4</volume><issue>3</issue><spage>868</spage><epage>880</epage><pages>868-880</pages><issn>1615-9853</issn><eissn>1615-9861</eissn><abstract>A proteomics approach combined with multivariate data analysis was used to examine the hepatotoxic effect of hydrazine in 30 male Sprague Dawley rats, assigned to four treatment groups and two control groups. Liver samples from the individual animals were resolved by two‐dimensional differential gel electrophoresis (2‐D DIGE) and protein patterns from the 2‐D gels were analyzed by principal component analysis (PCA) and partial least squares regression (PLSR). The PCA plot was able to describe the variation in the protein expression related to dose and time, by separation or clustering of different animal groups. PLSR followed by variable selection (Jack‐knifing) was used to select proteins that varied significantly in relation to the dose related response of the hydrazine treatment. The 10 up‐regulated and 10 down‐regulated proteins with highest rank in the PLSR model were identified by mass spectrometry. Hydrazine treatment induced altered expression of proteins related to lipid metabolism, Ca2+ homeostasis, thyroid hormone pathways and stress response. 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| subjects | Analytical, structural and metabolic biochemistry Animals Antineoplastic Agents - pharmacology Biological and medical sciences Biomarkers Calcium - metabolism Carcinogens Chemometrics Differential gel electrophoresis Dose-Response Relationship, Drug Down-Regulation Electrophoresis, Gel, Two-Dimensional - methods Fundamental and applied biological sciences. Psychology Hydrazine toxicity Hydrazines - pharmacology Hydrazines - toxicity Liver - drug effects Liver - metabolism Male Mass Spectrometry Miscellaneous Multivariate Analysis Peptides - chemistry Proteins Proteins - chemistry Proteome Proteomics - methods Rats Rats, Sprague-Dawley Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization Time Factors Up-Regulation |
| title | Mechanisms of hydrazine toxicity in rat liver investigated by proteomics and multivariate data analysis |
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