Loss of Intralipid®- but not sevoflurane-mediated cardioprotection in early type-2 diabetic hearts of fructose-fed rats: Importance of ROS signaling
| Autor: | Liyan Zhang, Hany F. Sobhi, Phing-How Lou, Andreas Affolter, Hélène Lemieux, Alexander S. Clanachan, Michael Zaugg, Blair E. Warren, Martin Hersberger, Manoj Gandhi, Eliana Lucchinetti |
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| Přispěvatelé: | University of Zurich |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Male
Critical Care and Emergency Medicine medicine.medical_treatment General Anesthesia lcsh:Medicine Bioinformatics Biochemistry Ion Channels Rats Sprague-Dawley chemistry.chemical_compound 0302 clinical medicine Anesthesiology Medicine and Health Sciences Uncoupling Protein 3 Anesthesia lcsh:Science General Inhalational Anesthesia Trauma Medicine Phospholipids Cardioprotection chemistry.chemical_classification 0303 health sciences Multidisciplinary Heart Type 2 Diabetes Reperfusion Injury Emulsions Research Article Signal Transduction medicine.drug Methyl Ethers Fat Emulsions Intravenous medicine.medical_specialty Cardiotonic Agents Cardiology Ischemia Myocardial Reperfusion Injury 610 Medicine & health Fructose 1100 General Agricultural and Biological Sciences Cardiovascular Pharmacology Sevoflurane Electron Transport Complex IV Mitochondrial Proteins 03 medical and health sciences Insulin resistance 1300 General Biochemistry Genetics and Molecular Biology Diabetes mellitus Internal medicine Diabetes Mellitus medicine Animals 030304 developmental biology Reactive oxygen species 1000 Multidisciplinary business.industry Insulin lcsh:R Biology and Life Sciences medicine.disease Rats Soybean Oil Metabolism Endocrinology Diabetes Mellitus Type 2 chemistry 10036 Medical Clinic Metabolic Disorders lcsh:Q Energy Metabolism Reactive Oxygen Species business 030217 neurology & neurosurgery |
| Zdroj: | PLoS ONE PLoS ONE, Vol 9, Iss 8, p e104971 (2014) |
| DOI: | 10.5167/uzh-98264 |
| Popis: | Background Insulin resistance and early type-2 diabetes are highly prevalent. However, it is unknown whether Intralipid® and sevoflurane protect the early diabetic heart against ischemia-reperfusion injury. Methods Early type-2 diabetic hearts from Sprague-Dawley rats fed for 6 weeks with fructose were exposed to 15 min of ischemia and 30 min of reperfusion. Intralipid® (1%) was administered at the onset of reperfusion. Peri-ischemic sevoflurane (2 vol.-%) served as alternative protection strategy. Recovery of left ventricular function was recorded and the activation of Akt and ERK 1/2 was monitored. Mitochondrial function was assessed by high-resolution respirometry and mitochondrial ROS production was measured by Amplex Red and aconitase activity assays. Acylcarnitine tissue content was measured and concentration-response curves of complex IV inhibition by palmitoylcarnitine were obtained. Results Intralipid® did not exert protection in early diabetic hearts, while sevoflurane improved functional recovery. Sevoflurane protection was abolished by concomitant administration of the ROS scavenger N-2-mercaptopropionyl glycine. Sevoflurane, but not Intralipid® produced protective ROS during reperfusion, which activated Akt. Intralipid® failed to inhibit respiratory complex IV, while sevoflurane inhibited complex I. Early diabetic hearts exhibited reduced carnitine-palmitoyl-transferase-1 activity, but palmitoylcarnitine could not rescue protection and enhance postischemic functional recovery. Cardiac mitochondria from early diabetic rats exhibited an increased content of subunit IV-2 of respiratory complex IV and of uncoupling protein-3. Conclusions Early type-2 diabetic hearts lose complex IV-mediated protection by Intralipid® potentially due to a switch in complex IV subunit expression and increased mitochondrial uncoupling, but are amenable to complex I-mediated sevoflurane protection. |
| Databáze: | OpenAIRE |
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