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Cardiolipin degradation during cardiac ischemia reperfusion injury: partial restoration by ranolazine
Author(s) -
Gadicherla Ashish K.,
Camara Amadou K.S.,
Yang Meiying,
Stowe David F.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.639.17
Cardiolipin (CL) is the major lipid in the inner mitochondrial membrane and hence plays a crucial role in maintaining protein structure in respiratory complexes. CL is susceptible to oxidative damage due to its large number of unsaturated bonds, so changes in CL elution profile are expected during high oxidative stress in cardiac ischemia reperfusion (IR) injury. We assessed changes in CL integrity after IR +/− ranolazine (Ran), a mitochondrial‐targeted drug. Lipids were isolated from guinea pig hearts exposed to one of 5 protocols: 30 min perfusion with KR buffer (KR), 30 min global ischemia (I30), I30+10 min reperfusion (IR), I30+Ran, and IR+Ran. Lipids were analyzed for CL by HPLC. We found that KR had one major species of CL, while I30 and IR had at least 2 added species, with the peak intensity for major species lower than for KR, and additional peaks eluting in close proximity to the major species. Ran treated groups showed a decreased intensity of additional species and a small increase in the major species. These findings may underlie our prior results showing a) decreased complex I and II activity after IR and restored activity with Ran, and b) disruption of super complexes during IR and restored assembly with Ran, suggesting that CL integrity is necessary for integrity of mitochondrial metabolic pathways, and Ran helps to preserve this integrity. Further studies are needed to determine how Ran preserves CL integrity.