Secondary inhibition of 2-ketoglutarate dehydrogenase complex by MPTP
The parkinsonism-inducing neurotoxin 1-methyl-4-phenylpyridine (MPP) acts through inhibition of complex I of the electron transport chain. Recent evidence suggests that it may also act through inhibition of 2-ketoglutarate dehydrogenase complex (KDHC). We confirmed this observation in isolated rat l...
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| Veröffentlicht in: | Neuroreport 1998-08, Vol.9 (12), p.2781-2783 |
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| creator | Joffe, Gabriella T Parks, Janice K Parker, W Davis |
| description | The parkinsonism-inducing neurotoxin 1-methyl-4-phenylpyridine (MPP) acts through inhibition of complex I of the electron transport chain. Recent evidence suggests that it may also act through inhibition of 2-ketoglutarate dehydrogenase complex (KDHC). We confirmed this observation in isolated rat liver mitochondria but found that this inhibition is prevented by preincubation with the radical quencher, cysteine (Cys). KDHC is also inhibited by the NO generator S-nitroso-N-acetyl-penicillamine (SNAP) and this inhibition is similarly blocked bycysteine. MPP may inhibit KDHC secondary through a radical-mediated event rather than through directinteraction with KDHC. |
| doi_str_mv | 10.1097/00001756-199808240-00018 |
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Recent evidence suggests that it may also act through inhibition of 2-ketoglutarate dehydrogenase complex (KDHC). We confirmed this observation in isolated rat liver mitochondria but found that this inhibition is prevented by preincubation with the radical quencher, cysteine (Cys). KDHC is also inhibited by the NO generator S-nitroso-N-acetyl-penicillamine (SNAP) and this inhibition is similarly blocked bycysteine. 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Recent evidence suggests that it may also act through inhibition of 2-ketoglutarate dehydrogenase complex (KDHC). We confirmed this observation in isolated rat liver mitochondria but found that this inhibition is prevented by preincubation with the radical quencher, cysteine (Cys). KDHC is also inhibited by the NO generator S-nitroso-N-acetyl-penicillamine (SNAP) and this inhibition is similarly blocked bycysteine. MPP may inhibit KDHC secondary through a radical-mediated event rather than through directinteraction with KDHC.</description><subject>1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine - pharmacology</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases</subject><subject>Dopamine Agents - pharmacology</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>In Vitro Techniques</subject><subject>Ketoglutarate Dehydrogenase Complex - antagonists & inhibitors</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mitochondria, Liver - drug effects</subject><subject>Neurology</subject><subject>Penicillamine - analogs & derivatives</subject><subject>Penicillamine - pharmacology</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Reactive Oxygen Species - physiology</subject><subject>S-Nitroso-N-Acetylpenicillamine</subject><subject>Sodium-Potassium-Exchanging ATPase - antagonists & inhibitors</subject><subject>Spectrophotometry, Ultraviolet</subject><issn>0959-4965</issn><issn>1473-558X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kc1uGyEURlHVyHHTPkKlWUTdTQMz_C6jKGkrOYqlOFJ2iGEu9jR4cGBGjt--uHbdVdgguOd-VxwQKgj-TrASVzgvIhgviVISy4ricn8jP6ApoaIuGZPPH9EUK6ZKqjg7R59S-p0RlaEJmijBManwFN0-gg19a-Ku6PpV13RDF_oiuKIqX2AISz8OJpoBihZWuzaGJfQmQWHDeuPhrWh2xf18Mf-MzpzxCb4c9wv0dHe7uPlZzh5-_Lq5npWWEiZLRZ1hrgUnJeGsNsK2VDopGiIAK1UxLjmIVtlGCSbzoW5wYw2vjFMUc1pfoG-H3E0MryOkQa-7ZMF700MYkyaC5AyiMigPoI0hpQhOb2K3zq_UBOu9Qf3PoD4Z1H8N5tavxxljs4b21HhUluuXx7pJ1ngXTW-79D-f1zWr9xg9YNvgB4jpxY9biHoFxg8r_d7_1X8Ar4eHXA</recordid><startdate>19980824</startdate><enddate>19980824</enddate><creator>Joffe, Gabriella T</creator><creator>Parks, Janice K</creator><creator>Parker, W Davis</creator><general>Lippincott-Raven Publishers</general><general>Lippincott Williams and Wilkins</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>19980824</creationdate><title>Secondary inhibition of 2-ketoglutarate dehydrogenase complex by MPTP</title><author>Joffe, Gabriella T ; Parks, Janice K ; Parker, W Davis</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4158-94fa5fdef881653a7cd48f87b17e09925686e7d9cb97586863b0bca62af940643</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine - pharmacology</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases</topic><topic>Dopamine Agents - pharmacology</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>In Vitro Techniques</topic><topic>Ketoglutarate Dehydrogenase Complex - antagonists & inhibitors</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mitochondria, Liver - drug effects</topic><topic>Neurology</topic><topic>Penicillamine - analogs & derivatives</topic><topic>Penicillamine - pharmacology</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Reactive Oxygen Species - physiology</topic><topic>S-Nitroso-N-Acetylpenicillamine</topic><topic>Sodium-Potassium-Exchanging ATPase - antagonists & inhibitors</topic><topic>Spectrophotometry, Ultraviolet</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Joffe, Gabriella T</creatorcontrib><creatorcontrib>Parks, Janice K</creatorcontrib><creatorcontrib>Parker, W Davis</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>Neuroreport</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Joffe, Gabriella T</au><au>Parks, Janice K</au><au>Parker, W Davis</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Secondary inhibition of 2-ketoglutarate dehydrogenase complex by MPTP</atitle><jtitle>Neuroreport</jtitle><addtitle>Neuroreport</addtitle><date>1998-08-24</date><risdate>1998</risdate><volume>9</volume><issue>12</issue><spage>2781</spage><epage>2783</epage><pages>2781-2783</pages><issn>0959-4965</issn><eissn>1473-558X</eissn><abstract>The parkinsonism-inducing neurotoxin 1-methyl-4-phenylpyridine (MPP) acts through inhibition of complex I of the electron transport chain. Recent evidence suggests that it may also act through inhibition of 2-ketoglutarate dehydrogenase complex (KDHC). We confirmed this observation in isolated rat liver mitochondria but found that this inhibition is prevented by preincubation with the radical quencher, cysteine (Cys). KDHC is also inhibited by the NO generator S-nitroso-N-acetyl-penicillamine (SNAP) and this inhibition is similarly blocked bycysteine. MPP may inhibit KDHC secondary through a radical-mediated event rather than through directinteraction with KDHC.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott-Raven Publishers</pub><pmid>9760120</pmid><doi>10.1097/00001756-199808240-00018</doi><tpages>3</tpages></addata></record> |
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| language | eng |
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| source | Journals@Ovid Ovid Autoload; MEDLINE |
| subjects | 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine - pharmacology Animals Biological and medical sciences Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases Dopamine Agents - pharmacology Enzyme Inhibitors - pharmacology In Vitro Techniques Ketoglutarate Dehydrogenase Complex - antagonists & inhibitors Male Medical sciences Mitochondria, Liver - drug effects Neurology Penicillamine - analogs & derivatives Penicillamine - pharmacology Rats Rats, Sprague-Dawley Reactive Oxygen Species - physiology S-Nitroso-N-Acetylpenicillamine Sodium-Potassium-Exchanging ATPase - antagonists & inhibitors Spectrophotometry, Ultraviolet |
| title | Secondary inhibition of 2-ketoglutarate dehydrogenase complex by MPTP |
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