Presentation is loading. Please wait.

Presentation is loading. Please wait.

Heart Mitochondrial Cardiolipin Oxidation during Ischemia in the Aged Rat E. Lesnefsky, P. Minkler, Charles Hoppel Case School of Medicine Louis Stokes.

Similar presentations


Presentation on theme: "Heart Mitochondrial Cardiolipin Oxidation during Ischemia in the Aged Rat E. Lesnefsky, P. Minkler, Charles Hoppel Case School of Medicine Louis Stokes."— Presentation transcript:

1 Heart Mitochondrial Cardiolipin Oxidation during Ischemia in the Aged Rat E. Lesnefsky, P. Minkler, Charles Hoppel Case School of Medicine Louis Stokes VA Medical Center

2 Paul Minkler Edward Lesnefsky, M.D. Paul Minkler Bernard Tandler, Ph.D. Shadi Moghaddas, Ph.D.Bernard Tandler, Ph.D. Qun Chen, M.D., Ph.D.Medhat Hassan, M.D. Edwin Vazquez Alessandro Riva, M.D., Ph.D. Funding:NIA Funding:NIA PO1 AG15885 Aging Heart: Basis of Increased Ischemic/Reflow Injury

3 Heart Mitochondrial Cardiolipin Oxidation during Ischemia in the Aged Rat IntroductionIntroduction Mitochondria in aging heartMitochondria in aging heart Mitochondrial Cardiolipin – ischemia in aging heartMitochondrial Cardiolipin – ischemia in aging heart SummarySummary

4 Increased Injury in Aging Heart Aging hearts showed increased injury:Aging hearts showed increased injury: –Decreased hemodynamic recovery –Increased CPK release-increased tissue damage Aging myocardium has an increased intrinsic susceptibility to damage during ischemia and reperfusionAging myocardium has an increased intrinsic susceptibility to damage during ischemia and reperfusion

5 Heart Mitochondrial Cardiolipin Oxidation during Ischemia in the Aged Rat IntroductionIntroduction Mitochondria in aging heartMitochondria in aging heart Mitochondrial Cardiolipin – ischemia in aging heartMitochondrial Cardiolipin – ischemia in aging heart SummarySummary

6 Cardiac Mitochondria Exist in Two Populations: Subsarcolemmal Mitochondria (SSM) and Interfibrillar Mitochondria (IFM) nucleus contractile proteins Interfibrillar Mitochondria in contractile regions Subsarcolemmal Mitochondria under cell membrane Cardiomyocyte Palmer et al. J Biol Chem 1977;252:

7 Heart Mitochondrial Cardiolipin Oxidation during Ischemia in the Aged Rat ProblemProblem Mitochondria in aging heartMitochondria in aging heart Mitochondrial Cardiolipin – ischemia in aging heartMitochondrial Cardiolipin – ischemia in aging heart SummarySummary

8 100% MEOH Series of iso-octane: ethyl acetate:HoAC washes Folch Extract Lipids Silica Gel Phospholipids (PE, PI,CL, PC) Quantification and Characterization of Cardiolipin Normal Phase HPLC

9

10

11 Aging Does not Alter Content of Cardiolipin SSM 6mo(n=9) IFM 6mo(n=9) 24mo(n=10) P=NS vs 6mo,   SEM nmol/mg protein Moghaddas et al. JGerontol Biol Sci 2002: 57:B22-28.

12

13 Content of Cardiolipin is Unaltered by Ischemia and Reperfusion in Adult and Aged Hearts mo n=5 24mo n=7 nmol/mg protein 6mo n=5 24mo n=7 p=NS,  SEM SSM IFM

14 OD 206 peak area ratio = 1496 peak /1448 peakOD 206 peak area ratio = 1496 peak /1448 peak Peaks identified by subsequent MSPeaks identified by subsequent MS Ischemia-Reperfusion Increases Relative Amount of Oxidized Cardiolipin in Aged Heart SSMIFM Ratio peak 6mo, n=4 24mo, n=6 * * *p<0.05vs 6mo,  SD

15 SSMIFM Ratio Peak 6mo, I-R n=4 24mo, I-R n=6 24mo, Isch n=4 *p<0.05vs 6mo,  SD * * * * Ischemia Alone Increases Relative Amount of Oxidized Cardiolipin in Aged Heart

16

17

18 MS Analysis of Oxidized Cardiolipin: Evidence of Linoleic Acid Oxidation O O O O O POOP O O O - OH H O OK O H O O O Native 4 C18:2 = m/z 1448

19 6mo IFM 24mo IFM Ischemia Increases Production of Oxidized Cardiolipin in Aged Heart 6mo 25min Ischemia, IFM 24mo 25min Ischemia, IFM HPLC/MS 1496 m/z RIC

20 Heart Mitochondrial Cardiolipin Oxidation during Ischemia in the Aged Rat ProblemProblem Mitochondria in aging heartMitochondria in aging heart Mitochondrial Cardiolipin – ischemia in aging heartMitochondrial Cardiolipin – ischemia in aging heart SummarySummary

21 Conclusions ^Oxidative damage to cardiolipin occurs in the ischemic- reperfused aged, but not the adult heart. ^Ischemia alone is sufficient to induce oxidative damage to cardiolipin in the aged rat heart. ^Cardiolipin modification provides evidence of enhanced oxidative damage to mitochondria during ischemia in the aged heart.


Download ppt "Heart Mitochondrial Cardiolipin Oxidation during Ischemia in the Aged Rat E. Lesnefsky, P. Minkler, Charles Hoppel Case School of Medicine Louis Stokes."

Similar presentations


Ads by Google