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Article: Propofol Ameliorates Hyperglycemia-Induced Cardiac Hypertrophy and Dysfunction via Heme Oxygenase-1/Signal Transducer and Activator of Transcription 3 Signaling Pathway in Rats

TitlePropofol Ameliorates Hyperglycemia-Induced Cardiac Hypertrophy and Dysfunction via Heme Oxygenase-1/Signal Transducer and Activator of Transcription 3 Signaling Pathway in Rats
Authors
KeywordsDiabetes
Heme oxygenase-1
Myocardial hypertrophy and dysfunction
Propofol
Signal transducer and activator of transcription 3
Issue Date2014
PublisherLippincott Williams & Wilkins. The Journal's web site is located at http://www.ccmjournal.org
Citation
Critical Care Medicine, 2014, v. 42 n. 8, p. e583-e594 How to Cite?
AbstractObjectives: Heme oxygenase-1 is inducible in cardiomyocytes in response to stimuli such as oxidative stress and plays critical roles in combating cardiac hypertrophy and injury. Signal transducer and activator of transcription 3 plays a pivotal role in heme oxygenase-1-mediated protection against liver and lung injuries under oxidative stress. We hypothesized that propofol, an anesthetic with antioxidant capacity, may attenuate hyperglycemia-induced oxidative stress in cardiomyocytes via enhancing heme oxygenase-1 activation and ameliorate hyperglycemia-induced cardiac hypertrophy and apoptosis via heme oxygenase-1/signal transducer and activator of transcription 3 signaling and improve cardiac function in diabetes. Design: Treatment study. Setting: Research laboratory. Subjects: Sprague-Dawley rats. Interventions: In vivo and in vitro treatments. Measurements and Main Results: At 8 weeks of streptozotocin-induced type 1 diabetes in rats, myocardial 15-F2t-isoprostane was significantly increased, accompanied by cardiomyocyte hypertrophy and apoptosis and impaired left ventricular function that was coincident with reduced heme oxygenase-1 activity and signal transducer and activator of transcription 3 activation despite an increase in heme oxygenase-1 protein expression as compared to control. Propofol infusion (900 μg/kg/min) for 45 minutes significantly improved cardiac function with concomitantly enhanced heme oxygenase-1 activity and signal transducer and activator of transcription activation. Similar to the changes seen in diabetic rat hearts, high glucose (25 mmol/L) exposure for 48 hours led to cardiomyocyte hypertrophy and apoptosis, both in primary cultured neonatal rat cardiomyocytes and in H9c2 cells compared to normal glucose (5.5 mmol/L). Hypertrophy was accompanied by increased reactive oxygen species and malondialdehyde production and caspase-3 activity. Propofol, similar to the heme oxygenase-1 inducer cobalt protoporphyrin, significantly increased cardiomyocyte heme oxygenase-1 and p-signal transducer and activator of transcription protein expression and heme oxygenase-1 activity and attenuated high-glucose-mediated cardiomyocyte hypertrophy and apoptosis and reduced reactive oxygen species and malondialdehyde production (p < 0.05). These protective effects of propofol were abolished by heme oxygenase-1 inhibition with zinc protoporphyrin and by heme oxygenase-1 or signal transducer and activator of transcription 3 gene knockdown. Conclusions: Heme oxygenase-1/signal transducer and activator of transcription 3 signaling plays a critical role in propofol-mediated amelioration of hyperglycemia-induced cardiomyocyte hypertrophy and apoptosis, whereby propofol improves cardiac function in diabetic rats.
Persistent Identifierhttp://hdl.handle.net/10722/202482
ISSN
2023 Impact Factor: 7.7
2023 SCImago Journal Rankings: 2.663
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorXu, J-
dc.contributor.authorLi, H-
dc.contributor.authorIrwin, MG-
dc.contributor.authorXia, ZY-
dc.contributor.authorMao, X-
dc.contributor.authorLei, S-
dc.contributor.authorWong, GT-
dc.contributor.authorHung, V-
dc.contributor.authorCheung, CW-
dc.contributor.authorFang, X-
dc.contributor.authorClanachan, AS-
dc.contributor.authorXia, Z-
dc.date.accessioned2014-09-19T07:59:40Z-
dc.date.available2014-09-19T07:59:40Z-
dc.date.issued2014-
dc.identifier.citationCritical Care Medicine, 2014, v. 42 n. 8, p. e583-e594-
dc.identifier.issn0090-3493-
dc.identifier.urihttp://hdl.handle.net/10722/202482-
dc.description.abstractObjectives: Heme oxygenase-1 is inducible in cardiomyocytes in response to stimuli such as oxidative stress and plays critical roles in combating cardiac hypertrophy and injury. Signal transducer and activator of transcription 3 plays a pivotal role in heme oxygenase-1-mediated protection against liver and lung injuries under oxidative stress. We hypothesized that propofol, an anesthetic with antioxidant capacity, may attenuate hyperglycemia-induced oxidative stress in cardiomyocytes via enhancing heme oxygenase-1 activation and ameliorate hyperglycemia-induced cardiac hypertrophy and apoptosis via heme oxygenase-1/signal transducer and activator of transcription 3 signaling and improve cardiac function in diabetes. Design: Treatment study. Setting: Research laboratory. Subjects: Sprague-Dawley rats. Interventions: In vivo and in vitro treatments. Measurements and Main Results: At 8 weeks of streptozotocin-induced type 1 diabetes in rats, myocardial 15-F2t-isoprostane was significantly increased, accompanied by cardiomyocyte hypertrophy and apoptosis and impaired left ventricular function that was coincident with reduced heme oxygenase-1 activity and signal transducer and activator of transcription 3 activation despite an increase in heme oxygenase-1 protein expression as compared to control. Propofol infusion (900 μg/kg/min) for 45 minutes significantly improved cardiac function with concomitantly enhanced heme oxygenase-1 activity and signal transducer and activator of transcription activation. Similar to the changes seen in diabetic rat hearts, high glucose (25 mmol/L) exposure for 48 hours led to cardiomyocyte hypertrophy and apoptosis, both in primary cultured neonatal rat cardiomyocytes and in H9c2 cells compared to normal glucose (5.5 mmol/L). Hypertrophy was accompanied by increased reactive oxygen species and malondialdehyde production and caspase-3 activity. Propofol, similar to the heme oxygenase-1 inducer cobalt protoporphyrin, significantly increased cardiomyocyte heme oxygenase-1 and p-signal transducer and activator of transcription protein expression and heme oxygenase-1 activity and attenuated high-glucose-mediated cardiomyocyte hypertrophy and apoptosis and reduced reactive oxygen species and malondialdehyde production (p < 0.05). These protective effects of propofol were abolished by heme oxygenase-1 inhibition with zinc protoporphyrin and by heme oxygenase-1 or signal transducer and activator of transcription 3 gene knockdown. Conclusions: Heme oxygenase-1/signal transducer and activator of transcription 3 signaling plays a critical role in propofol-mediated amelioration of hyperglycemia-induced cardiomyocyte hypertrophy and apoptosis, whereby propofol improves cardiac function in diabetic rats.-
dc.languageeng-
dc.publisherLippincott Williams & Wilkins. The Journal's web site is located at http://www.ccmjournal.org-
dc.relation.ispartofCritical Care Medicine-
dc.subjectDiabetes-
dc.subjectHeme oxygenase-1-
dc.subjectMyocardial hypertrophy and dysfunction-
dc.subjectPropofol-
dc.subjectSignal transducer and activator of transcription 3-
dc.titlePropofol Ameliorates Hyperglycemia-Induced Cardiac Hypertrophy and Dysfunction via Heme Oxygenase-1/Signal Transducer and Activator of Transcription 3 Signaling Pathway in Rats-
dc.typeArticle-
dc.identifier.emailXu, J: xushiwei@hku.hk-
dc.identifier.emailIrwin, MG: mgirwin@hku.hk-
dc.identifier.emailMao, X: susanmao@hku.hk-
dc.identifier.emailLei, S: shqlei@hku.hk-
dc.identifier.emailWong, GT: gordon@hku.hk-
dc.identifier.emailCheung, CW: cheucw@hku.hk-
dc.identifier.emailXia, Z: zyxia@hkucc.hku.hk-
dc.identifier.authorityIrwin, MG=rp00390-
dc.identifier.authorityMao, X=rp02828-
dc.identifier.authorityWong, GT=rp00523-
dc.identifier.authorityCheung, CW=rp00244-
dc.identifier.authorityXia, Z=rp00532-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1097/CCM.0000000000000415-
dc.identifier.pmid24810525-
dc.identifier.scopuseid_2-s2.0-84904733302-
dc.identifier.hkuros235557-
dc.identifier.hkuros261688-
dc.identifier.volume42-
dc.identifier.issue8-
dc.identifier.spagee583-
dc.identifier.epagee594-
dc.identifier.isiWOS:000339330700004-
dc.publisher.placeUnited States-
dc.identifier.issnl0090-3493-

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