In:
Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 95, No. 7 ( 2004-10), p. 734-741
Abstract:
The antiapoptotic protein Bcl-2 is targeted to the mitochondria, but it is uncertain whether Bcl-2 affects only myocyte survival after ischemia, or whether it also affects metabolic functions of mitochondria during ischemia. Hearts from mice overexpressing human Bcl-2 and from their wild-type littermates (WT) were subjected to 24 minutes of global ischemia followed by reperfusion. During ischemia, the decrease in pH i and the initial rate of decline in ATP were significantly reduced in Bcl-2 hearts compared with WT hearts ( P 〈 0.05). The reduced acidification during ischemia was dependent on the activity of mitochondrial F 1 F 0 -ATPase. In the presence of oligomycin (Oligo), an F 1 F 0 -ATPase inhibitor, the decrease in pH i was attenuated in WT hearts, but in Bcl-2 hearts, Oligo had no additional effect on pH i during ischemia. Likewise, addition of Oligo to WT hearts slowed the rate of decline in ATP during ischemia to a level similar to that observed in Bcl-2 hearts, but addition of Oligo had no significant effect on the rate of decline in ATP in Bcl-2 hearts during ischemia. These data are consistent with Bcl-2–mediated inhibition of consumption of glycolytic ATP. Furthermore, mitochondria from Bcl-2 hearts have a reduced rate of consumption of ATP on uncoupler addition. This could be accomplished by limiting ATP entry into the mitochondria through the voltage-dependent anion channel, and/or the adenine nucleotide transporter, or by direct inhibition of the F 1 F 0 -ATPase. Immunoprecipitation showed greater interaction between Bcl-2 and voltage-dependent anion channel during ischemia. These data indicate that Bcl-2 modulation of metabolism contributes to cardioprotection.
Type of Medium:
Online Resource
ISSN:
0009-7330
,
1524-4571
DOI:
10.1161/01.RES.0000143898.67182.4c
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2004
detail.hit.zdb_id:
1467838-X
