Difference between revisions of "Power 2016 Am J Physiol Heart Circ Physiol"

Revision as of 15:25, 17 January 2023

Power AS, Pham T, Loiselle DS, Crossman DH, Ward ML, Hickey AJ (2016) Impaired ADP channeling to mitochondria and elevated reactive oxygen species in hypertensive hearts. https://doi.org/10.1152/ajpheart.00050.2016

» Am J Physiol Heart Circ Physiol 310:H1649-57. PMID: 27084386 Open Access

Power Amelia SC, Pham Toan, Loiselle Denis S, Crossman David H, Ward Marie-Louise, Hickey Anthony J (2016) Am J Physiol Heart Circ Physiol

Abstract: Systemic hypertension initially promotes a compensatory cardiac hypertrophy, yet it progresses to heart failure (HF), and energetic deficits appear to be central to this failure. However, the transfer of energy between the mitochondria and the myofibrils is not often considered as part of the energetic equation. We compared hearts from old spontaneously hypertensive rats (SHRs) and normotensive Wistar controls. SHR hearts showed a 35% depression in mitochondrial function, yet produced at least double the amount of reactive oxygen species (ROS) in all respiration states in left ventricular (LV) homogenates. To test the connectivity between mitochondria and myofibrils, respiration was further tested in situ with LV permeabilized fibers by addition of multiple substrates and ATP, which requires hydrolysis to mediate oxidative phosphorylation. By trapping ADP using a pyruvate kinase enzyme system, we tested ADP channeling towards mitochondria, and this suppressed respiration and elevated ROS production more in the SHR fibers. The ADP-trapped state was also less relieved on creatine addition, likely reflecting the 30% depression in total CK activity in the SHR heart fibers. Confocal imaging identified a 34% longer distance between the centers of myofibril to mitochondria in the SHR hearts, which increases transverse metabolite diffusion distances (e.g., for ATP, ADP, and creatine phosphate). We propose that impaired connectivity between mitochondria and myofibrils may contribute to elevated ROS production. Impaired energy exchange could be the result of ultrastructural changes that occur with hypertrophy in this model of hypertension. • Keywords: Creatine shuttle, Hypertrophy, Mitochondria, Oxidative phosphorylation, Reactive oxygen species • Bioblast editor: Plangger M

Labels: MiParea: Respiration

Organism: Rat Tissue;cell: Heart Preparation: Permeabilized tissue

HRR: Oxygraph-2k

2023-01

@@ Line 2: / Line 2: @@
 |title=Power AS, Pham T, Loiselle DS, Crossman DH, Ward ML, Hickey AJ (2016) Impaired ADP channeling to mitochondria and elevated reactive oxygen species in hypertensive hearts. https://doi.org/10.1152/ajpheart.00050.2016
 |info=Am J Physiol Heart Circ Physiol 310:H1649-57. [https://pubmed.ncbi.nlm.nih.gov/27084386 PMID: 27084386 Open Access]
-|authors=Power AS, Pham T, Loiselle DS, Crossman DH, Ward ML, Hickey AJ
+|authors=Power Amelia SC, Pham Toan, Loiselle Denis S, Crossman David H, Ward Marie-Louise, Hickey Anthony J
 |year=2016
 |journal=Am J Physiol Heart Circ Physiol
-|abstract=Systemic hypertension initially promotes a compensatory cardiac hypertrophy, yet it progresses to heart failure (HF), and energetic deficits appear to be central to this failure. However, the transfer of energy between the mitochondria and the myofibrils is not often considered as part of the energetic equation. We compared hearts from old spontaneously hypertensive rats (SHRs) and normotensive Wistar controls. SHR hearts showed a 35% depression in mitochondrial function, yet produced at least double the amount of reactive oxygen species (ROS) in all respiration states in left ventricular (LV) homogenates. To test the connectivity between mitochondria and myofibrils, respiration was further tested in situ with LV permeabilized fibers by addition of multiple substrates and ATP, which requires hydrolysis to mediate oxidative phosphorylation. By trapping ADP using a pyruvate kinase enzyme system, we tested ADP channeling towards mitochondria, and this suppressed respiration and elevated ROS production more in the SHR fibers. The ADP-trapped state was also less relieved on creatine addition, likely reflecting the 30% depression in total CK activity in the SHR heart fibers. Confocal imaging identified a 34% longer distance between the centers of myofibril to mitochondria in the SHR hearts, which increases transverse metabolite diffusion distances (e.g., for ATP, ADP, and creatine phosphate). We propose that impaired connectivity between mitochondria and myofibrils may contribute to elevated ROS production. Impaired energy exchange could be the result of ultrastructural changes that occur with hypertrophy in this model of hypertension.
+|abstract=Systemic hypertension initially promotes a compensatory cardiac hypertrophy, yet it progresses to heart failure (HF), and energetic deficits appear to be central to this failure. However, the transfer of energy between the mitochondria and the myofibrils is not often considered as part of the energetic equation. We compared hearts from old spontaneously hypertensive rats (SHRs) and normotensive Wistar controls. SHR hearts showed a 35% depression in mitochondrial function, yet produced at least double the amount of reactive oxygen species (ROS) in all respiration states in left ventricular (LV) homogenates. To test the connectivity between mitochondria and myofibrils, respiration was further tested ''in situ'' with LV permeabilized fibers by addition of multiple substrates and ATP, which requires hydrolysis to mediate oxidative phosphorylation. By trapping ADP using a pyruvate kinase enzyme system, we tested ADP channeling towards mitochondria, and this suppressed respiration and elevated ROS production more in the SHR fibers. The ADP-trapped state was also less relieved on creatine addition, likely reflecting the 30% depression in total CK activity in the SHR heart fibers. Confocal imaging identified a 34% longer distance between the centers of myofibril to mitochondria in the SHR hearts, which increases transverse metabolite diffusion distances (e.g., for ATP, ADP, and creatine phosphate). We propose that impaired connectivity between mitochondria and myofibrils may contribute to elevated ROS production. Impaired energy exchange could be the result of ultrastructural changes that occur with hypertrophy in this model of hypertension.
 |keywords=Creatine shuttle, Hypertrophy, Mitochondria, Oxidative phosphorylation, Reactive oxygen species
 |editor=[[Plangger M]]
@@ Line 11: / Line 11: @@
 {{Labeling
 |area=Respiration
+|organism=Rat
+|tissues=Heart
+|preparations=Permeabilized tissue
 |instruments=Oxygraph-2k
 |additional=2023-01
 }}