{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:44:50Z","timestamp":1760402690263,"version":"build-2065373602"},"reference-count":34,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hong Kong Research Grant Council","award":["ERGC-HKU7248\/99M"],"award-info":[{"award-number":["ERGC-HKU7248\/99M"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["NeuroSci"],"abstract":"<jats:p>Transmembrane 29 (Tmem29) gene with unknown function is a gene located on the X chromosome of the mouse genome. The gene showed differential expression in the Vannucci neonatal hypoxic-ischemic mouse brain model. We found the gene expresses with different molecular forms, including a group of long non-coding RNA forming a family of transcripts. It was predominantly expressed in the testes, brain, and kidney of mouse. In vitro identification and functional characterization were carried out in Neuro2a cells. Using fluorescence microscopy, Tmem29 protein was found to be constitutively expressed in mouse cell lines of different origins. Oxygen glucose deprivation (OGD) induced apoptotic cell death in Neuro2a cells and was confirmed by activations of caspase 3. Tmem29 protein was found to be associated with cell death especially at the time points of caspase 3 activations. A similar response was obtained in glucose deprivation (GD) cultures suggesting Tmem29 response to a common mechanism induced by OGD and GD. Downregulation of Tmem29 was induced by OGD and GD, further validating its response to hypoxia-ischemia (HI) insults. Our findings contributed to further understanding of molecular events after hypoxic-ischemic insults and opens new avenues for developing protective and therapeutic strategies for hypoxic-ischemic encephalopathy or even pathological programmed cell death.<\/jats:p>","DOI":"10.3390\/neurosci3010003","type":"journal-article","created":{"date-parts":[[2022,1,9]],"date-time":"2022-01-09T20:21:56Z","timestamp":1641759716000},"page":"41-51","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Transmembrane 29 (Tmem29), a Newly Identified Molecule Showed Downregulation in Hypoxic-Ischemic Brain Damage"],"prefix":"10.3390","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6066-5333","authenticated-orcid":false,"given":"Hing-Wai","family":"Tsang","sequence":"first","affiliation":[{"name":"Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3417-1185","authenticated-orcid":false,"given":"Inderjeet","family":"Bhatia","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koon-Wing","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Godfrey Chi-Fung","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6797-6898","authenticated-orcid":false,"given":"Patrick","family":"Ip","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China"},{"name":"Room 123, 1\/F, New Clinical Building, Queen Mary Hospital, Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pik-To","family":"Cheung","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China"},{"name":"5\/F, Virtus Medical Tower, 122 Queen\u2019s Road Central, Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1985","DOI":"10.1056\/NEJMra041996","article-title":"Neonatal brain injury","volume":"351","author":"Ferriero","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1053\/j.semperi.2004.10.003","article-title":"Brain injury in the term infant","volume":"28","author":"Perlman","year":"2004","journal-title":"Semin. Perinatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1001\/archneur.1976.00500100030012","article-title":"Neonatal encephalopathy following fetal distress. A clinical and electroencephalographic study","volume":"33","author":"Sarnat","year":"1976","journal-title":"Arch. Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1111\/j.1651-2227.1997.tb08581.x","article-title":"The value of a scoring system for hypoxic ischaemic encephalopathy in predicting neurodevelopmental outcome","volume":"86","author":"Thompson","year":"1997","journal-title":"Acta Paediatr."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.4103\/1673-5374.217338","article-title":"Effect of erythropoietin combined with hypothermia on serum tau protein levels and neurodevelopmental outcome in neonates with hypoxic-ischemic encephalopathy","volume":"12","author":"Lv","year":"2017","journal-title":"Neural Regen. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.ejpn.2020.04.003","article-title":"Minor neurological signs and behavioural function at age 2 years in neonatal hypoxic ischaemic encephalopathy (HIE)","volume":"27","author":"Edmonds","year":"2020","journal-title":"Eur. J. Paediatr. Neurol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.expneurol.2014.07.009","article-title":"Detecting brain injury in neonatal hypoxic ischemic encephalopathy: Closing the gap between experimental and clinical research","volume":"261","author":"Aridas","year":"2014","journal-title":"Exp. Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Arteaga, O., Revuelta, M., Uriguen, L., Alvarez, A., Montalvo, H., and Hilario, E. (2015). Pretreatment with Resveratrol Prevents Neuronal Injury and Cognitive Deficits Induced by Perinatal Hypoxia-Ischemia in Rats. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0142424"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"15","DOI":"10.3233\/JAD-170589","article-title":"Hypoxia-Induced Signaling Activation in Neurodegenerative Diseases: Targets for New Therapeutic Strategies","volume":"62","author":"Jha","year":"2018","journal-title":"J. Alzheim. Dis."},{"key":"ref_10","unstructured":"(2021, June 23). National Center for Biotechnology Information (NCBI) GENE Database, Available online: https:\/\/www.ncbi.nlm.nih.gov\/gene\/382245."},{"key":"ref_11","unstructured":"(2021, June 23). The European Bioinformatics Institute(EMBL-EBI), Ensembl Mouse Gene Database. Available online: https:\/\/asia.ensembl.org\/Mus_musculus\/Gene\/Summary?db=core;g=ENSMUSG00000041353;r=X:149180769-149242150."},{"key":"ref_12","unstructured":"(2021, July 04). National Center for Biotechnology Information (NCBI) HomoloGene Database (Accession no.:136288), Available online: https:\/\/www.ncbi.nlm.nih.gov\/homologene\/136288."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Reinius, B., Johansson, M.M., Radomska, K.J., Morrow, E.H., Pandey, G.K., Kanduri, C., Sandberg, R., Williams, R.W., and Jazin, E. (2012). Abundance of female-biased and paucity of male-biased somatically expressed genes on the mouse X-chromosome. BMC Genom., 13.","DOI":"10.1186\/1471-2164-13-607"},{"key":"ref_14","first-page":"1","article-title":"Anoxic-ischemic encephalopathy in rats","volume":"36","author":"Levine","year":"1960","journal-title":"Am. J. Pathol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1002\/ana.410090206","article-title":"The influence of immaturity on hypoxic-ischemic brain damage in the rat","volume":"9","author":"Rice","year":"1981","journal-title":"Ann. Neurol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1002\/(SICI)1097-4547(19990115)55:2<158::AID-JNR3>3.0.CO;2-1","article-title":"Rat model of perinatal hypoxic-ischemic brain damage","volume":"55","author":"Vannucci","year":"1999","journal-title":"J. Neurosci. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1111\/j.1749-6632.1997.tb48634.x","article-title":"A model of perinatal hypoxic-ischemic brain damage","volume":"835","author":"Vannucci","year":"1997","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Nguyen, B.A.N., Pogoutse, A., Provart, N., and Moses, A.M. (2009). NLStradamus: A simple Hidden Markov Model for nuclear localization signal prediction. BMC Bioinf., 10.","DOI":"10.1186\/1471-2105-10-202"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1002\/ana.1073","article-title":"Microarray analysis of hippocampal gene expression in global cerebral ischemia","volume":"50","author":"Jin","year":"2001","journal-title":"Ann. Neurol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/S0361-9230(02)00823-7","article-title":"DNA array reveals altered gene expression in response to focal cerebral ischemia","volume":"58","author":"Kim","year":"2002","journal-title":"Brain. Res. Bull."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1046\/j.1471-4159.2002.01208.x","article-title":"Gene expression analysis of spontaneously hypertensive rat cerebral cortex following transient focal cerebral ischemia","volume":"83","author":"Bowen","year":"2002","journal-title":"J. Neurochem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1937","DOI":"10.1046\/j.1460-9568.2002.02030.x","article-title":"Genomic responses of the brain to ischemic stroke, intracerebral haemorrhage, kainate seizures, hypoglycemia, and hypoxia","volume":"15","author":"Tang","year":"2002","journal-title":"Eur. J. Neurosci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/0169-328X(93)90194-T","article-title":"Immediate early gene induction after neonatal hypoxia-ischemia","volume":"18","author":"Gubits","year":"1993","journal-title":"Brain. Res. Mol. Brain. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1097\/00004647-200412000-00002","article-title":"Global gene expression in the immature brain after hypoxia-ischemia","volume":"24","author":"Hedtjarn","year":"2004","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1212\/WNL.48.2.306","article-title":"Ischemic tolerance in the brain","volume":"48","author":"Chen","year":"1997","journal-title":"Neurology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1152\/physrev.1992.72.4.1063","article-title":"Mammalian stress response: Cell physiology, structure\/function of stress proteins, and implications for medicine and disease","volume":"72","author":"Welch","year":"1992","journal-title":"Physiol. Rev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.1126\/science.1138341","article-title":"RNA maps reveal new RNA classes and a possible function for pervasive transcription","volume":"316","author":"Kapranov","year":"2007","journal-title":"Science"},{"key":"ref_28","unstructured":"(2019). 6 Non-coding RNA characterization. Nature."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.brainresbull.2019.06.004","article-title":"Long non-coding RNA MALAT1 sponges microRNA-429 to regulate apoptosis of hippocampal neurons in hypoxic-ischemic brain damage by regulating WNT1","volume":"152","author":"Fang","year":"2019","journal-title":"Brain. Res. Bull"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11010-020-03754-2","article-title":"Silencing of long non-coding RNA CRNDE promotes autophagy and alleviates neonatal hypoxic-ischemic brain damage in rats","volume":"472","author":"Fu","year":"2020","journal-title":"Mol. Cell Biochem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1111\/jnc.14689","article-title":"Analysis of long non-coding RNA expression profiles in neonatal rats with hypoxic-ischemic brain damage","volume":"149","author":"Zhou","year":"2019","journal-title":"J. Neurochem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e2911","DOI":"10.1038\/cddis.2017.299","article-title":"Autophagy fails to prevent glucose deprivation\/glucose reintroduction-induced neuronal death due to calpain-mediated lysosomal dysfunction in cortical neurons","volume":"8","author":"Montiel","year":"2017","journal-title":"Cell Death Dis."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.pneurobio.2018.01.001","article-title":"Autophagy in ischemic stroke","volume":"163\u2013164","author":"Wang","year":"2018","journal-title":"Prog. Neurobiol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Zhao, M., Zhu, P., Fujino, M., Zhuang, J., Guo, H., Sheikh, I., Zhao, L., and Li, X.K. (2016). Oxidative Stress in Hypoxic-Ischemic Encephalopathy: Molecular Mechanisms and Therapeutic Strategies. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17122078"}],"container-title":["NeuroSci"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2673-4087\/3\/1\/3\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:59:51Z","timestamp":1760363991000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2673-4087\/3\/1\/3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,1]]},"references-count":34,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,3]]}},"alternative-id":["neurosci3010003"],"URL":"https:\/\/doi.org\/10.3390\/neurosci3010003","relation":{},"ISSN":["2673-4087"],"issn-type":[{"type":"electronic","value":"2673-4087"}],"subject":[],"published":{"date-parts":[[2022,1,1]]}}}