{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T21:03:11Z","timestamp":1792098191860,"version":"4.4.0"},"reference-count":55,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2013,6,12]],"date-time":"2013-06-12T00:00:00Z","timestamp":1370995200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2013,7]]},"abstract":"Background and Purpose<\/jats:title>H<\/jats:styled-content>igh\u2010altitude pulmonary oedema (HAPE<\/jats:styled-content>) experienced under high\u2010altitude conditions is attributed to mitochondrial redox distress. Hence, hypobaric hypoxia (HH<\/jats:styled-content>)\u2010induced alteration in expression of mitochondrial biogenesis and dynamics genes was determined in rat lung. Further, such alteration was correlated with expression of mitochondrial DNA<\/jats:styled-content> (mtDNA<\/jats:styled-content>)\u2010encoded oxidative phosphorylation (mtOXPHOS<\/jats:styled-content>) genes. The prophylactic effect of dexamethasone (DEX<\/jats:styled-content>) in counteracting the HH<\/jats:styled-content>\u2010induced mitochondrial distress was used as control to understand adaptation to high\u2010altitude exposure.<\/jats:p><\/jats:sec>Experimental Approach<\/jats:title>Rats pretreated with DEX<\/jats:styled-content> were exposed to normobaric normoxia (NN<\/jats:styled-content>) or HH<\/jats:styled-content>. HH<\/jats:styled-content>\u2010induced injury was assessed as an increase in lung water content, tissue damage and oxidant generation. Mitochondrial number, mtDNA<\/jats:styled-content> content and mtOXPHOS<\/jats:styled-content> activities were measured to determine mitochondrial function. The expression of mitochondrial biogenesis, dynamics and mtOXPHOS<\/jats:styled-content> genes was studied.<\/jats:p><\/jats:sec>Key Results<\/jats:title>HH<\/jats:styled-content>\u2010induced lung injury was associated with decreased mitochondrial number, mtDNA<\/jats:styled-content> content and mtOXPHOS<\/jats:styled-content> activities. HH<\/jats:styled-content> exposure decreased the nuclear gene oestrogen\u2010related receptor\u2010\u03b1 (ERR<\/jats:styled-content>\u03b1),<\/jats:styled-content> which interacts with PPAR\u2010\u03b3 coactivator\u20101<\/jats:styled-content>\u03b1 (PGC<\/jats:styled-content>\u20101\u03b1)<\/jats:styled-content> in controlling mitochondrial metabolism. Consequently, mtOXPHOS<\/jats:styled-content> transcripts are repressed under HH<\/jats:styled-content>. Further, HH<\/jats:styled-content> modulated mitochondrial dynamics by decreasing mitofusin 2 (Mfn2)<\/jats:styled-content> and augmenting fission 1 (Fis1)<\/jats:styled-content> and dynamin\u2010related protein 1 (Drp1)<\/jats:styled-content> expression. Nevertheless, DEX<\/jats:styled-content> treatment under NN<\/jats:styled-content> (i.e. adaptation to HH<\/jats:styled-content>) did not affect mitochondrial biogenesis and dynamics, but increased mtOXPHOS<\/jats:styled-content> transcripts. Further, mtOXPHOS<\/jats:styled-content> activities increased together with reduced oxidant generation. Also, DEX<\/jats:styled-content> pretreatment normalized ERR<\/jats:styled-content>\u03b1 along with mitochondrial dynamics genes and increased mtOXPHOS<\/jats:styled-content> transcripts to elicit the mitochondrial function under HH<\/jats:styled-content>.<\/jats:p><\/jats:sec>Conclusions and Implications<\/jats:title>HH<\/jats:styled-content> stress (HAPE<\/jats:styled-content>)\u2010mediated mitochondrial dysfunction is due to repressed ERR<\/jats:styled-content>\u03b1 and mtOXPHOS<\/jats:styled-content> transcripts. Thus, ERR<\/jats:styled-content>\u03b1\u2010mediated protection of <\/jats:styled-content>mitochondrial bioenergetics might be the likely candidate required for lung adaptation to HH<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.12179","type":"journal-article","created":{"date-parts":[[2013,3,20]],"date-time":"2013-03-20T13:49:46Z","timestamp":1363787386000},"page":"1035-1047","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Adaptability to hypobaric hypoxia is facilitated through mitochondrial bioenergetics: an in vivo<\/i> study"],"prefix":"10.1111","volume":"169","author":[{"given":"Loganathan","family":"Chitra","sequence":"first","affiliation":[{"name":"Molecular Biology and Biotechnology Division DRDO \u2013 BU Center for Life Sciences Bharathiar University Coimbatore India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rathanam","family":"Boopathy","sequence":"additional","affiliation":[{"name":"Department of Biotechnology Bharathiar University Coimbatore India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,6,12]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-0102(00)00188-7"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1580\/0953-9859-1.3.162"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.03381"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-006-0640-3"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0076-6879(95)60134-1"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2005.092031"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2008.08.007"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1871610"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.02.026"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00486070"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1982.62.1.262"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2009.08.007"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddh109"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2007.04.001"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1113\/eph8802514"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2011.10.491"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00338.2006"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5654-07.2008"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80319-0"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200406-707OC"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.111.174128"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.med.47.1.267"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2007.06.005"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M303758200"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2006.078873"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0024-3205(97)00193-8"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.06-0573"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.109.212753"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2010.00872.x"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/0009-8981(94)90270-4"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20100596"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)52451-6"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2010.00873.x"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.01324.2004"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.103.16.2078"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-145-7-200610030-00007"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2005.02.008"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-6-267"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0401401101"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1119(01)00814-9"},{"key":"e_1_2_9_42_1","unstructured":"PfafflMW(2009).Rest 2009 Software User Guide. Qiagen Hilden Germany. Available at:http:\/\/b2b.qiagen.com\/products\/rest2009software.aspx(accessed 14\/12\/2009)."},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddi149"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2011.05.014"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2009.12.006"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1113\/eph8802507"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0308686101"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2011.01.038"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2008.10.025"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.143.2.351"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI113800"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1991.70.4.1731"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80611-X"},{"key":"e_1_2_9_54_1","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1152\/jappl.1986.60.5.1665","article-title":"Dexamethasone increases adult rat lung surfactant lipids","volume":"60","author":"Young SL","year":"1986","journal-title":"J Appl Physiol"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0703397"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00806.2006"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fbph.12179","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.12179","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T02:52:50Z","timestamp":1697424770000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bph.12179"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,6,12]]},"references-count":55,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2013,7]]}},"alternative-id":["10.1111\/bph.12179"],"URL":"https:\/\/doi.org\/10.1111\/bph.12179","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,6,12]]},"assertion":[{"value":"2012-09-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-03-06","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-06-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}