Increase in Cardiac Ischemia-Reperfusion Injuries in Opa1+/- Mouse Model.
Recent data suggests the involvement of mitochondrial dynamics in cardiac ischemia/reperfusion (I/R) injuries. Whilst excessive mitochondrial fission has been described as detrimental, the role of fusion proteins in this context remains uncertain.To investigate whether Opa1 (protein involved in mito...
| Main Authors: | , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2016-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5056696?pdf=render |
| _version_ | 1828397223808860160 |
|---|---|
| author | Sophie Le Page Marjorie Niro Jérémy Fauconnier Laura Cellier Sophie Tamareille Abdallah Gharib Arnaud Chevrollier Laurent Loufrani Céline Grenier Rima Kamel Emmanuelle Sarzi Alain Lacampagne Michel Ovize Daniel Henrion Pascal Reynier Guy Lenaers Delphine Mirebeau-Prunier Fabrice Prunier |
| author_facet | Sophie Le Page Marjorie Niro Jérémy Fauconnier Laura Cellier Sophie Tamareille Abdallah Gharib Arnaud Chevrollier Laurent Loufrani Céline Grenier Rima Kamel Emmanuelle Sarzi Alain Lacampagne Michel Ovize Daniel Henrion Pascal Reynier Guy Lenaers Delphine Mirebeau-Prunier Fabrice Prunier |
| author_sort | Sophie Le Page |
| collection | DOAJ |
| description | Recent data suggests the involvement of mitochondrial dynamics in cardiac ischemia/reperfusion (I/R) injuries. Whilst excessive mitochondrial fission has been described as detrimental, the role of fusion proteins in this context remains uncertain.To investigate whether Opa1 (protein involved in mitochondrial inner-membrane fusion) deficiency affects I/R injuries.We examined mice exhibiting Opa1delTTAG mutations (Opa1+/-), showing 70% Opa1 protein expression in the myocardium as compared to their wild-type (WT) littermates. Cardiac left-ventricular systolic function assessed by means of echocardiography was observed to be similar in 3-month-old WT and Opa1+/- mice. After subjection to I/R, infarct size was significantly greater in Opa1+/- than in WTs both in vivo (43.2±4.1% vs. 28.4±3.5%, respectively; p<0.01) and ex vivo (71.1±3.2% vs. 59.6±8.5%, respectively; p<0.05). No difference was observed in the expression of other main fission/fusion protein, oxidative phosphorylation, apoptotic markers, or mitochondrial permeability transition pore (mPTP) function. Analysis of calcium transients in isolated ventricular cardiomyocytes demonstrated a lower sarcoplasmic reticulum Ca2+ uptake, whereas cytosolic Ca2+ removal from the Na+/Ca2+ exchanger (NCX) was increased, whilst SERCA2a, phospholamban, and NCX protein expression levels were unaffected in Opa1+/- compared to WT mice. Simultaneous whole-cell patch-clamp recordings of mitochondrial Ca2+ movements and ventricular action potential (AP) showed impairment of dynamic mitochondrial Ca2+ uptake and a marked increase in the AP late repolarization phase in conjunction with greater occurrence of arrhythmia in Opa1+/- mice.Opa1 deficiency was associated with increased sensitivity to I/R, imbalance in dynamic mitochondrial Ca2+ uptake, and subsequent increase in NCX activity. |
| first_indexed | 2024-12-10T08:42:54Z |
| format | Article |
| id | doaj.art-9a94a432c8f143a69675a6b6f979acba |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T08:42:54Z |
| publishDate | 2016-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-9a94a432c8f143a69675a6b6f979acba2022-12-22T01:55:47ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-011110e016406610.1371/journal.pone.0164066Increase in Cardiac Ischemia-Reperfusion Injuries in Opa1+/- Mouse Model.Sophie Le PageMarjorie NiroJérémy FauconnierLaura CellierSophie TamareilleAbdallah GharibArnaud ChevrollierLaurent LoufraniCéline GrenierRima KamelEmmanuelle SarziAlain LacampagneMichel OvizeDaniel HenrionPascal ReynierGuy LenaersDelphine Mirebeau-PrunierFabrice PrunierRecent data suggests the involvement of mitochondrial dynamics in cardiac ischemia/reperfusion (I/R) injuries. Whilst excessive mitochondrial fission has been described as detrimental, the role of fusion proteins in this context remains uncertain.To investigate whether Opa1 (protein involved in mitochondrial inner-membrane fusion) deficiency affects I/R injuries.We examined mice exhibiting Opa1delTTAG mutations (Opa1+/-), showing 70% Opa1 protein expression in the myocardium as compared to their wild-type (WT) littermates. Cardiac left-ventricular systolic function assessed by means of echocardiography was observed to be similar in 3-month-old WT and Opa1+/- mice. After subjection to I/R, infarct size was significantly greater in Opa1+/- than in WTs both in vivo (43.2±4.1% vs. 28.4±3.5%, respectively; p<0.01) and ex vivo (71.1±3.2% vs. 59.6±8.5%, respectively; p<0.05). No difference was observed in the expression of other main fission/fusion protein, oxidative phosphorylation, apoptotic markers, or mitochondrial permeability transition pore (mPTP) function. Analysis of calcium transients in isolated ventricular cardiomyocytes demonstrated a lower sarcoplasmic reticulum Ca2+ uptake, whereas cytosolic Ca2+ removal from the Na+/Ca2+ exchanger (NCX) was increased, whilst SERCA2a, phospholamban, and NCX protein expression levels were unaffected in Opa1+/- compared to WT mice. Simultaneous whole-cell patch-clamp recordings of mitochondrial Ca2+ movements and ventricular action potential (AP) showed impairment of dynamic mitochondrial Ca2+ uptake and a marked increase in the AP late repolarization phase in conjunction with greater occurrence of arrhythmia in Opa1+/- mice.Opa1 deficiency was associated with increased sensitivity to I/R, imbalance in dynamic mitochondrial Ca2+ uptake, and subsequent increase in NCX activity.http://europepmc.org/articles/PMC5056696?pdf=render |
| spellingShingle | Sophie Le Page Marjorie Niro Jérémy Fauconnier Laura Cellier Sophie Tamareille Abdallah Gharib Arnaud Chevrollier Laurent Loufrani Céline Grenier Rima Kamel Emmanuelle Sarzi Alain Lacampagne Michel Ovize Daniel Henrion Pascal Reynier Guy Lenaers Delphine Mirebeau-Prunier Fabrice Prunier Increase in Cardiac Ischemia-Reperfusion Injuries in Opa1+/- Mouse Model. PLoS ONE |
| title | Increase in Cardiac Ischemia-Reperfusion Injuries in Opa1+/- Mouse Model. |
| title_full | Increase in Cardiac Ischemia-Reperfusion Injuries in Opa1+/- Mouse Model. |
| title_fullStr | Increase in Cardiac Ischemia-Reperfusion Injuries in Opa1+/- Mouse Model. |
| title_full_unstemmed | Increase in Cardiac Ischemia-Reperfusion Injuries in Opa1+/- Mouse Model. |
| title_short | Increase in Cardiac Ischemia-Reperfusion Injuries in Opa1+/- Mouse Model. |
| title_sort | increase in cardiac ischemia reperfusion injuries in opa1 mouse model |
| url | http://europepmc.org/articles/PMC5056696?pdf=render |
| work_keys_str_mv | AT sophielepage increaseincardiacischemiareperfusioninjuriesinopa1mousemodel AT marjorieniro increaseincardiacischemiareperfusioninjuriesinopa1mousemodel AT jeremyfauconnier increaseincardiacischemiareperfusioninjuriesinopa1mousemodel AT lauracellier increaseincardiacischemiareperfusioninjuriesinopa1mousemodel AT sophietamareille increaseincardiacischemiareperfusioninjuriesinopa1mousemodel AT abdallahgharib increaseincardiacischemiareperfusioninjuriesinopa1mousemodel AT arnaudchevrollier increaseincardiacischemiareperfusioninjuriesinopa1mousemodel AT laurentloufrani increaseincardiacischemiareperfusioninjuriesinopa1mousemodel AT celinegrenier increaseincardiacischemiareperfusioninjuriesinopa1mousemodel AT rimakamel increaseincardiacischemiareperfusioninjuriesinopa1mousemodel AT emmanuellesarzi increaseincardiacischemiareperfusioninjuriesinopa1mousemodel AT alainlacampagne increaseincardiacischemiareperfusioninjuriesinopa1mousemodel AT michelovize increaseincardiacischemiareperfusioninjuriesinopa1mousemodel AT danielhenrion increaseincardiacischemiareperfusioninjuriesinopa1mousemodel AT pascalreynier increaseincardiacischemiareperfusioninjuriesinopa1mousemodel AT guylenaers increaseincardiacischemiareperfusioninjuriesinopa1mousemodel AT delphinemirebeauprunier increaseincardiacischemiareperfusioninjuriesinopa1mousemodel AT fabriceprunier increaseincardiacischemiareperfusioninjuriesinopa1mousemodel |