Oxidative Damage of DJ-1 Is Linked to Sporadic Parkinson and Alzheimer Diseases
Mutations in DJ-1 cause an autosomal recessive, early onset familial form of Parkinson disease (PD). However, little is presently known about the role of DJ-1 in the more common sporadic form of PD and in other age-related neurodegenerative diseases, such as Alzheimer disease (AD). Here we report th...
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| Veröffentlicht in: | The Journal of biological chemistry 2006-04, Vol.281 (16), p.10816-10824 |
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| creator | Choi, Joungil Sullards, M. Cameron Olzmann, James A. Rees, Howard D. Weintraub, Susan T. Bostwick, David E. Gearing, Marla Levey, Allan I. Chin, Lih-Shen Li, Lian |
| description | Mutations in DJ-1 cause an autosomal recessive, early onset familial form of Parkinson disease (PD). However, little is presently known about the role of DJ-1 in the more common sporadic form of PD and in other age-related neurodegenerative diseases, such as Alzheimer disease (AD). Here we report that DJ-1 is oxidatively damaged in the brains of patients with idiopathic PD and AD. By using a combination of two-dimensional gel electrophoresis and mass spectrometry, we have identified 10 different DJ-1 isoforms, of which the acidic isoforms (pI 5.5 and 5.7) of DJ-1 monomer and the basic isoforms (pI 8.0 and 8.4) of SDS-resistant DJ-1 dimer are selectively accumulated in PD and AD frontal cortex tissues compared with age-matched controls. Quantitative Western blot analysis shows that the total level of DJ-1 protein is significantly increased in PD and AD brains. Mass spectrometry analyses reveal that DJ-1 is not only susceptible to cysteine oxidation but also to previously unsuspected methionine oxidation. Furthermore, we show that DJ-1 protein is irreversibly oxidized by carbonylation as well as by methionine oxidation to methionine sulfone in PD and AD. Our study provides new insights into the oxidative modifications of DJ-1 and indicates association of oxidative damage to DJ-1 with sporadic PD and AD. |
| doi_str_mv | 10.1074/jbc.M509079200 |
| format | Article |
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Cameron ; Olzmann, James A. ; Rees, Howard D. ; Weintraub, Susan T. ; Bostwick, David E. ; Gearing, Marla ; Levey, Allan I. ; Chin, Lih-Shen ; Li, Lian</creator><creatorcontrib>Choi, Joungil ; Sullards, M. Cameron ; Olzmann, James A. ; Rees, Howard D. ; Weintraub, Susan T. ; Bostwick, David E. ; Gearing, Marla ; Levey, Allan I. ; Chin, Lih-Shen ; Li, Lian</creatorcontrib><description>Mutations in DJ-1 cause an autosomal recessive, early onset familial form of Parkinson disease (PD). However, little is presently known about the role of DJ-1 in the more common sporadic form of PD and in other age-related neurodegenerative diseases, such as Alzheimer disease (AD). Here we report that DJ-1 is oxidatively damaged in the brains of patients with idiopathic PD and AD. By using a combination of two-dimensional gel electrophoresis and mass spectrometry, we have identified 10 different DJ-1 isoforms, of which the acidic isoforms (pI 5.5 and 5.7) of DJ-1 monomer and the basic isoforms (pI 8.0 and 8.4) of SDS-resistant DJ-1 dimer are selectively accumulated in PD and AD frontal cortex tissues compared with age-matched controls. Quantitative Western blot analysis shows that the total level of DJ-1 protein is significantly increased in PD and AD brains. Mass spectrometry analyses reveal that DJ-1 is not only susceptible to cysteine oxidation but also to previously unsuspected methionine oxidation. Furthermore, we show that DJ-1 protein is irreversibly oxidized by carbonylation as well as by methionine oxidation to methionine sulfone in PD and AD. Our study provides new insights into the oxidative modifications of DJ-1 and indicates association of oxidative damage to DJ-1 with sporadic PD and AD.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1074/jbc.M509079200</identifier><identifier>PMID: 16517609</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>2,4-Dinitrophenol - chemistry ; Aged ; Aged, 80 and over ; Alzheimer Disease - pathology ; Amino Acid Sequence ; Blotting, Western ; Brain - metabolism ; Brain - pathology ; Carbon - chemistry ; Cerebral Cortex - pathology ; Dimerization ; Electrophoresis, Gel, Two-Dimensional ; Female ; Humans ; Intracellular Signaling Peptides and Proteins ; Isoelectric Point ; Lipid Peroxidation ; Lipids - chemistry ; Male ; Mass Spectrometry ; Methionine - chemistry ; Middle Aged ; Molecular Sequence Data ; Neurodegenerative Diseases ; Oncogene Proteins - metabolism ; Oncogene Proteins - physiology ; Oxidative Stress ; Oxygen - chemistry ; Oxygen - metabolism ; Parkinson Disease - metabolism ; Parkinson Disease - pathology ; Peptides - chemistry ; Protein Deglycase DJ-1 ; Protein Isoforms ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Time Factors</subject><ispartof>The Journal of biological chemistry, 2006-04, Vol.281 (16), p.10816-10824</ispartof><rights>2006 © 2006 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c566t-adb33d9362729191591a08c08d2dd6ee10a48d4d9f08f7b20e86595b35fe3e223</citedby><cites>FETCH-LOGICAL-c566t-adb33d9362729191591a08c08d2dd6ee10a48d4d9f08f7b20e86595b35fe3e223</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1850953/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1850953/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16517609$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Choi, Joungil</creatorcontrib><creatorcontrib>Sullards, M. Cameron</creatorcontrib><creatorcontrib>Olzmann, James A.</creatorcontrib><creatorcontrib>Rees, Howard D.</creatorcontrib><creatorcontrib>Weintraub, Susan T.</creatorcontrib><creatorcontrib>Bostwick, David E.</creatorcontrib><creatorcontrib>Gearing, Marla</creatorcontrib><creatorcontrib>Levey, Allan I.</creatorcontrib><creatorcontrib>Chin, Lih-Shen</creatorcontrib><creatorcontrib>Li, Lian</creatorcontrib><title>Oxidative Damage of DJ-1 Is Linked to Sporadic Parkinson and Alzheimer Diseases</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>Mutations in DJ-1 cause an autosomal recessive, early onset familial form of Parkinson disease (PD). However, little is presently known about the role of DJ-1 in the more common sporadic form of PD and in other age-related neurodegenerative diseases, such as Alzheimer disease (AD). Here we report that DJ-1 is oxidatively damaged in the brains of patients with idiopathic PD and AD. By using a combination of two-dimensional gel electrophoresis and mass spectrometry, we have identified 10 different DJ-1 isoforms, of which the acidic isoforms (pI 5.5 and 5.7) of DJ-1 monomer and the basic isoforms (pI 8.0 and 8.4) of SDS-resistant DJ-1 dimer are selectively accumulated in PD and AD frontal cortex tissues compared with age-matched controls. Quantitative Western blot analysis shows that the total level of DJ-1 protein is significantly increased in PD and AD brains. Mass spectrometry analyses reveal that DJ-1 is not only susceptible to cysteine oxidation but also to previously unsuspected methionine oxidation. Furthermore, we show that DJ-1 protein is irreversibly oxidized by carbonylation as well as by methionine oxidation to methionine sulfone in PD and AD. Our study provides new insights into the oxidative modifications of DJ-1 and indicates association of oxidative damage to DJ-1 with sporadic PD and AD.</description><subject>2,4-Dinitrophenol - chemistry</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Alzheimer Disease - pathology</subject><subject>Amino Acid Sequence</subject><subject>Blotting, Western</subject><subject>Brain - metabolism</subject><subject>Brain - pathology</subject><subject>Carbon - chemistry</subject><subject>Cerebral Cortex - pathology</subject><subject>Dimerization</subject><subject>Electrophoresis, Gel, Two-Dimensional</subject><subject>Female</subject><subject>Humans</subject><subject>Intracellular Signaling Peptides and Proteins</subject><subject>Isoelectric Point</subject><subject>Lipid Peroxidation</subject><subject>Lipids - chemistry</subject><subject>Male</subject><subject>Mass Spectrometry</subject><subject>Methionine - chemistry</subject><subject>Middle Aged</subject><subject>Molecular Sequence Data</subject><subject>Neurodegenerative Diseases</subject><subject>Oncogene Proteins - metabolism</subject><subject>Oncogene Proteins - physiology</subject><subject>Oxidative Stress</subject><subject>Oxygen - chemistry</subject><subject>Oxygen - metabolism</subject><subject>Parkinson Disease - metabolism</subject><subject>Parkinson Disease - pathology</subject><subject>Peptides - chemistry</subject><subject>Protein Deglycase DJ-1</subject><subject>Protein Isoforms</subject><subject>Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization</subject><subject>Time Factors</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0c1v0zAYBvAIgVgZXDmCD4hbil8nTuwL0rTyMVRUpDGJm-XYbxpvSdzZafn46zFKxeCA8MUH__zotZ8sewp0CbQuX103ZvmRU0lrySi9ly2AiiIvOHy5ny0oZZBLxsVJ9ijGa5pWKeFhdgIVh7qicpFtNt-c1ZM7IFnpQW-R-JasPuRALiJZu_EGLZk8udz5oK0z5JMON26MfiR6tOSs_9GhGzCQlYuoI8bH2YNW9xGfHPfT7Ortm8_n7_P15t3F-dk6N7yqplzbpiisLCpWMwkSuARNhaHCMmsrRKC6FLa0sqWirRtGUVRc8qbgLRbIWHGavZ5zd_tmQGtwnILu1S64QYfvymun_j4ZXae2_qBApN_iRQp4eQwI_naPcVKDiwb7Xo_o91FVtagZL8V_IdRQylrSBJczNMHHGLD9PQ1Q9asslcpSd2WlC8_-fMMdP7aTwIsZdG7bfXUBVeO86XBQTEBiKVVAldjzmbXaK70NLqqrS0ahoEArUXNIQswCUyUHh0FF43A0aFOomZT17l9D_gTGB7b2</recordid><startdate>20060421</startdate><enddate>20060421</enddate><creator>Choi, Joungil</creator><creator>Sullards, M. 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Cameron ; Olzmann, James A. ; Rees, Howard D. ; Weintraub, Susan T. ; Bostwick, David E. ; Gearing, Marla ; Levey, Allan I. ; Chin, Lih-Shen ; Li, Lian</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c566t-adb33d9362729191591a08c08d2dd6ee10a48d4d9f08f7b20e86595b35fe3e223</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>2,4-Dinitrophenol - chemistry</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Alzheimer Disease - pathology</topic><topic>Amino Acid Sequence</topic><topic>Blotting, Western</topic><topic>Brain - metabolism</topic><topic>Brain - pathology</topic><topic>Carbon - chemistry</topic><topic>Cerebral Cortex - pathology</topic><topic>Dimerization</topic><topic>Electrophoresis, Gel, Two-Dimensional</topic><topic>Female</topic><topic>Humans</topic><topic>Intracellular Signaling Peptides and Proteins</topic><topic>Isoelectric Point</topic><topic>Lipid Peroxidation</topic><topic>Lipids - chemistry</topic><topic>Male</topic><topic>Mass Spectrometry</topic><topic>Methionine - chemistry</topic><topic>Middle Aged</topic><topic>Molecular Sequence Data</topic><topic>Neurodegenerative Diseases</topic><topic>Oncogene Proteins - metabolism</topic><topic>Oncogene Proteins - physiology</topic><topic>Oxidative Stress</topic><topic>Oxygen - chemistry</topic><topic>Oxygen - metabolism</topic><topic>Parkinson Disease - metabolism</topic><topic>Parkinson Disease - pathology</topic><topic>Peptides - chemistry</topic><topic>Protein Deglycase DJ-1</topic><topic>Protein Isoforms</topic><topic>Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization</topic><topic>Time Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Choi, Joungil</creatorcontrib><creatorcontrib>Sullards, M. Cameron</creatorcontrib><creatorcontrib>Olzmann, James A.</creatorcontrib><creatorcontrib>Rees, Howard D.</creatorcontrib><creatorcontrib>Weintraub, Susan T.</creatorcontrib><creatorcontrib>Bostwick, David E.</creatorcontrib><creatorcontrib>Gearing, Marla</creatorcontrib><creatorcontrib>Levey, Allan I.</creatorcontrib><creatorcontrib>Chin, Lih-Shen</creatorcontrib><creatorcontrib>Li, Lian</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>AGRIS</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><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Choi, Joungil</au><au>Sullards, M. Cameron</au><au>Olzmann, James A.</au><au>Rees, Howard D.</au><au>Weintraub, Susan T.</au><au>Bostwick, David E.</au><au>Gearing, Marla</au><au>Levey, Allan I.</au><au>Chin, Lih-Shen</au><au>Li, Lian</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Oxidative Damage of DJ-1 Is Linked to Sporadic Parkinson and Alzheimer Diseases</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>2006-04-21</date><risdate>2006</risdate><volume>281</volume><issue>16</issue><spage>10816</spage><epage>10824</epage><pages>10816-10824</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><abstract>Mutations in DJ-1 cause an autosomal recessive, early onset familial form of Parkinson disease (PD). However, little is presently known about the role of DJ-1 in the more common sporadic form of PD and in other age-related neurodegenerative diseases, such as Alzheimer disease (AD). Here we report that DJ-1 is oxidatively damaged in the brains of patients with idiopathic PD and AD. By using a combination of two-dimensional gel electrophoresis and mass spectrometry, we have identified 10 different DJ-1 isoforms, of which the acidic isoforms (pI 5.5 and 5.7) of DJ-1 monomer and the basic isoforms (pI 8.0 and 8.4) of SDS-resistant DJ-1 dimer are selectively accumulated in PD and AD frontal cortex tissues compared with age-matched controls. Quantitative Western blot analysis shows that the total level of DJ-1 protein is significantly increased in PD and AD brains. Mass spectrometry analyses reveal that DJ-1 is not only susceptible to cysteine oxidation but also to previously unsuspected methionine oxidation. Furthermore, we show that DJ-1 protein is irreversibly oxidized by carbonylation as well as by methionine oxidation to methionine sulfone in PD and AD. Our study provides new insights into the oxidative modifications of DJ-1 and indicates association of oxidative damage to DJ-1 with sporadic PD and AD.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>16517609</pmid><doi>10.1074/jbc.M509079200</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 2,4-Dinitrophenol - chemistry Aged Aged, 80 and over Alzheimer Disease - pathology Amino Acid Sequence Blotting, Western Brain - metabolism Brain - pathology Carbon - chemistry Cerebral Cortex - pathology Dimerization Electrophoresis, Gel, Two-Dimensional Female Humans Intracellular Signaling Peptides and Proteins Isoelectric Point Lipid Peroxidation Lipids - chemistry Male Mass Spectrometry Methionine - chemistry Middle Aged Molecular Sequence Data Neurodegenerative Diseases Oncogene Proteins - metabolism Oncogene Proteins - physiology Oxidative Stress Oxygen - chemistry Oxygen - metabolism Parkinson Disease - metabolism Parkinson Disease - pathology Peptides - chemistry Protein Deglycase DJ-1 Protein Isoforms Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization Time Factors |
| title | Oxidative Damage of DJ-1 Is Linked to Sporadic Parkinson and Alzheimer Diseases |
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