{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T04:31:46Z","timestamp":1762144306402},"reference-count":57,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2004,8,23]],"date-time":"2004-08-23T00:00:00Z","timestamp":1093219200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2004,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Trichloroethylene, a common industrial solvent and a metabolic precursor of chloral hydrate, occurs widely in the environment. Chloral hydrate, which is also used as a hypnotic, has been found to condense spontaneously with tryptamine, <jats:italic>in vivo<\/jats:italic>, to give rise to a highly unpolar 1\u2010trichloromethyl\u20101,2,3,4\u2010tetrahydro\u2010\u03b2\u2010carboline (TaClo) that has a structural analogy to the dopaminergic neurotoxin <jats:italic>N<\/jats:italic>\u2010methyl\u20104\u2010phenyl\u20101,2,3,6\u2010tetrahydropyridine (MPTP). Earlier studies have revealed the relative permeability of the molecule through the blood\u2013brain barrier and its ability to induce Parkinson\u2010like symptoms in rats. In this study, we report that TaClo induces an apoptotic pathway in the human neuroblastoma cell line, SK\u2010N\u2010SH, involving the translocation of mitochondrial cytochrome <jats:italic>c<\/jats:italic> to the cytosol and activation of caspase 3. TaClo\u2010induced apoptosis shows considerable differences from that mediated by other Parkinson\u2010inducing agents such as MPTP, rotenone and manganese. Although it is not clear if the clinically administered dosage of chloral hydrate or the relatively high environmental levels of trichloroethylene could lead to an onset of Parkinson's disease, the spontaneous <jats:italic>in vivo<\/jats:italic> formation of TaClo and its pro\u2010apoptotic properties, as shown in this report, should be considered.<\/jats:p>","DOI":"10.1111\/j.1471-4159.2004.02710.x","type":"journal-article","created":{"date-parts":[[2004,9,24]],"date-time":"2004-09-24T12:55:31Z","timestamp":1096030531000},"page":"263-273","source":"Crossref","is-referenced-by-count":24,"title":["1\u2010trichloromethyl\u20101,2,3,4\u2010tetrahydro\u2010\u03b2\u2010carboline\u2010induced apoptosis in the human neuroblastoma cell line SK\u2010N\u2010SH"],"prefix":"10.1111","volume":"91","author":[{"given":"Ravi Shankar","family":"Akundi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Macho","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eduardo","family":"Mu\u00f1oz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Klaus","family":"Lieb","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerhard","family":"Bringmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans\u2010Willi","family":"Clement","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"H\u00fcll","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernd L.","family":"Fiebich","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2004,9,10]]},"reference":[{"key":"e_1_2_22_2_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2003.02068.x"},{"key":"e_1_2_22_3_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2002.01047.x"},{"key":"e_1_2_22_4_1","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1299.053"},{"key":"e_1_2_22_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.23.9368"},{"key":"e_1_2_22_6_1","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1542\/peds.92.3.471","article-title":"Use of chloral hydrate for sedation in children","volume":"92","author":"American Academy of Pediatrics Committee on Drugs and Committee on Environmental Health","year":"1993","journal-title":"Pediatrics"},{"key":"e_1_2_22_7_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-05-01738.2002"},{"key":"e_1_2_22_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/81834"},{"key":"e_1_2_22_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ardp.19903230903"},{"key":"e_1_2_22_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1570-0232(01)00589-X"},{"key":"e_1_2_22_11_1","doi-asserted-by":"publisher","DOI":"10.1080\/10408440091159202"},{"key":"e_1_2_22_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(87)90021-2"},{"key":"e_1_2_22_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2042-7158.1975.tb09431.x"},{"key":"e_1_2_22_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/00006565-200002000-00001"},{"key":"e_1_2_22_15_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1087753"},{"key":"e_1_2_22_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0005-2728(98)00029-2"},{"key":"e_1_2_22_17_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.144.5.891"},{"key":"e_1_2_22_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0005-2728(03)00005-7"},{"key":"e_1_2_22_19_1","doi-asserted-by":"publisher","DOI":"10.1159\/000026225"},{"key":"e_1_2_22_20_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.281.5381.1309"},{"key":"e_1_2_22_21_1","doi-asserted-by":"publisher","DOI":"10.2214\/ajr.161.3.8352124"},{"key":"e_1_2_22_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(96)00785-5"},{"key":"e_1_2_22_23_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1468-1331.1999.650609.x"},{"key":"e_1_2_22_24_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.20.13432"},{"key":"e_1_2_22_25_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.040556597"},{"key":"e_1_2_22_26_1","doi-asserted-by":"publisher","DOI":"10.1021\/jf030324h"},{"key":"e_1_2_22_27_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2003.01533.x"},{"key":"e_1_2_22_28_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1998.275.5.H1567"},{"key":"e_1_2_22_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/352244a0"},{"key":"e_1_2_22_30_1","first-page":"265","article-title":"1\u2010Trichloromethyl\u20101,2,3,4\u2010tetrahydro\u2010beta\u2010carboline, a new inhibitor of complex I","volume":"46","author":"Janetzky B.","year":"1995","journal-title":"J. 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