Lou 2014b PLoS One

From Bioblast
Publications in the MiPMap
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 


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