{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T09:46:19Z","timestamp":1768038379620,"version":"3.49.0"},"reference-count":57,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2020,4,27]],"date-time":"2020-04-27T00:00:00Z","timestamp":1587945600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81771391"],"award-info":[{"award-number":["81771391"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2020,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Ketone bodies (KBs) were known to suppress seizure. Untraditionally, neurons were recently reported to utilize fatty acids and produce KBs, but the effect of seizure on neuronal ketogenesis has not been researched. Zinc\u2010\u03b12\u2010glycoprotein (ZAG) was reported to suppress seizure via unclear mechanism. Interestingly, ZAG was involved in fatty acid \u03b2\u2010oxidation and thus may exert anti\u2010epileptic effect by promoting ketogenesis. However, this promotive effect of ZAG on neuronal ketogenesis has not been clarified. In this study, we performed immunoprecipitation and mass spectrometry to identify potential interaction partners with ZAG. The mechanisms of how ZAG translocated into mitochondria were determined by quantitative coimmunoprecipitation after treatment with apoptozole, a heat shock cognate protein 70 (HSC70) inhibitor. ZAG level was modulated by lentivirus in neurons or adeno\u2010associated virus in rat brains. Seizure models were induced by magnesium (Mg<jats:sup>2+<\/jats:sup>)\u2010free artificial cerebrospinal fluid in neurons or intraperitoneal injection of pentylenetetrazole kindling in rats. Ketogenesis was determined by cyclic thio\u2010NADH method in supernatant of neurons or brain homogenate. The effect of peroxisome proliferator\u2013activated receptor \u03b3 (PPAR\u03b3) on ZAG expression was examined by Western blot, quantitative real\u2010time polymerase chain reaction (qRT\u2010PCR) and chromatin immunoprecipitation qRT\u2010PCR. We found that seizure induced ketogenesis deficiency via a ZAG\u2010dependent mechanism. ZAG entered mitochondria through a HSC70\u2010dependent mechanism, promoted ketogenesis by binding to four \u03b2\u2010subunits of long\u2010chain L\u20103\u2010hydroxyacyl\u2010CoA dehydrogenase (HADHB) and alleviated ketogenesis impairment in a neuronal seizure model and pentylenetetrazole\u2010kindled epileptic rats. Additionally, PPAR\u03b3 activation up\u2010regulated ZAG expression by binding to promoter region of <jats:italic>AZGP1<\/jats:italic> gene and promoted ketogenesis through a ZAG\u2010dependent mechanism.<\/jats:p>","DOI":"10.1111\/jcmm.15337","type":"journal-article","created":{"date-parts":[[2020,4,27]],"date-time":"2020-04-27T23:54:04Z","timestamp":1588031644000},"page":"6833-6845","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Seizure\u2010induced impairment in neuronal ketogenesis: Role of zinc\u2010\u03b12\u2010glycoprotein in mitochondria"],"prefix":"10.1111","volume":"24","author":[{"given":"Changhong","family":"Tan","sequence":"first","affiliation":[{"name":"Department of Neurology The Second Affiliated Hospital of Chongqing Medical University Chongqing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology The Second Affiliated Hospital of Chongqing Medical University Chongqing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wuxue","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Neurology The Second Affiliated Hospital of Chongqing Medical University Chongqing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology The Second Affiliated Hospital of Chongqing Medical University Chongqing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Neurology The Second Affiliated Hospital of Chongqing Medical University Chongqing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Neurology The Second Affiliated Hospital of Chongqing Medical University Chongqing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Neurology The Second Affiliated Hospital of Chongqing Medical University Chongqing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lijuan","family":"Mo","sequence":"additional","affiliation":[{"name":"Department of Neurology The Second Affiliated Hospital of Chongqing Medical University Chongqing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yangmei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology The Second Affiliated Hospital of Chongqing Medical University Chongqing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3355-1338","authenticated-orcid":false,"given":"Lifen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology The Second Affiliated Hospital of Chongqing Medical University Chongqing China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,4,27]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-017-2253-5"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(17)30408-8"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.490180407"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1177\/1759091414550997"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2010.09.002"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13718"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2005.04.014"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa1299"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12264-018-00332-x"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2017.05.043"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.13642"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-018-1132-6"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2016.06.003"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1159\/000339065"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2012.02.026"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0004(96)80163-0"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.4161\/auto.26448"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/332800a0"},{"key":"e_1_2_9_20_1","doi-asserted-by":"crossref","first-page":"11069","DOI":"10.1016\/S0021-9258(19)38558-8","article-title":"Mitochondrial precursor protein. 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