Lou 2014b PLoS One

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Lou PH, Lucchinetti E, Zhang L, Affolter A, Gandhi M, Hersberger M, Warren BE, Lemieux H, Sobhi HF, Clanachan AS, Zaugg M (2014) Loss of Intralipid®- but not sevoflurane-mediated cardioprotection in early type-2 diabetic hearts of fructose-fed rats: importance of ROS signaling. PLoS One 9:e104971.

» PMID:25127027

Lou PH, Lucchinetti E, Zhang L, Affolter A, Gandhi M, Hersberger M, Warren BE, Lemieux H, Sobhi HF, Clanachan AS, Zaugg M (2014) PLoS One

Abstract: 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.

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.

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.

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.

Keywords: Amplex Red

O2k-Network Lab: CA Edmonton Lemieux H, CA Edmonton Zaugg M


Labels: MiParea: Respiration, Pharmacology;toxicology  Pathology: Diabetes  Stress:Ischemia-reperfusion  Organism: Rat  Tissue;cell: Heart  Preparation: Permeabilized tissue 


Coupling state: LEAK  Pathway: F, N, S, CIV  HRR: Oxygraph-2k