Effects of oligomycin and acidosis on rates of ATP depletion in ischemic heart muscle

Rouslin, William; Erickson, Jay C.; Solaro, R. John

doi:10.1152/ajpheart.1986.250.3.h503

Cited by 61 publications

(46 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…19 Furthermore, during ischemia, the F 1 F 0 -ATPase consumes glycolytic ATP, thus contributing to depletion of ATP and cytosolic acidification caused by increased generation of lactate. 15,16 We find that Bcl-2 slows the rate of decline in ATP and reduces ischemic acidification during ischemia, consistent with Bcl-2 induced inhibition of consumption of glycolytically generated ATP. This could be accomplished by Bcl-2 induced closure of VDAC, closure of ANT, or inhibition of F 1 F 0 -ATPase.…”

Section: Discussionsupporting

confidence: 76%

“…Oligomycin has been reported to decrease acidification during ischemia because it blocks the breakdown of glycolytic ATP. 15 We reasoned that if the effects of Bcl-2 were mediated by a pathway that included the F 1 F 0 -ATPase, then the reduced acidification observed with Bcl-2 and oligomycin should not be additive. We selected an oligomycin concentration that was in the lower range of those previously used 16 (Ϸ3 mol/ L), and it was administered for 4 minutes before ischemia.…”

Section: Effect Of F 1 F 0 -Atpase Inhibition During Ischemiamentioning

confidence: 99%

“…During ischemia, when lack of oxygen inhibits mitochondrial electron transport and mitochondrial generation of ATP, the F 1 F 0 -ATP can run in reverse and consume glycolytically generated ATP. [15][16][17][18][19] In fact, many cells contain a natural inhibitor of the F 1 F 0 -ATPase, which binds the F 1 F 0 -ATPase during ischemia to inhibit breakdown of glycolytic ATP. 20 There are also data showing that ischemia and anoxia lead to a preferential decrease in cytosolic versus mitochondrial ATP, 21,22 suggesting that cells may regulate mitochondrial ADP/ATP exchange during ischemia.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Transgenic Expression of Bcl-2 Modulates Energy Metabolism, Prevents Cytosolic Acidification During Ischemia, and Reduces Ischemia/Reperfusion Injury

Imahashi

Schneider

Steenbergen

et al. 2004

Circulation Research

180

147

View full text Add to dashboard Cite

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 (PϽ0.05). 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.

show abstract

Section: Discussionsupporting

confidence: 76%

Section: Effect Of F 1 F 0 -Atpase Inhibition During Ischemiamentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Transgenic Expression of Bcl-2 Modulates Energy Metabolism, Prevents Cytosolic Acidification During Ischemia, and Reduces Ischemia/Reperfusion Injury

Imahashi

Schneider

Steenbergen

et al. 2004

Circulation Research

180

147

View full text Add to dashboard Cite

show abstract

“…Most of the consumption occurs in the mitochondria via the action of the mitochondrial ATPase. 39,40 Because of ATP utilization, the concentration of ADP rises. The HEP of ADP is captured by adenylate kinase which converts ADP to ATP and AMP.…”

Section: Metabolic Changesmentioning

confidence: 99%

Historical Perspective on the Pathology of Myocardial Ischemia/Reperfusion Injury

Jennings

2013

Circulation Research

213

194

View full text Add to dashboard Cite

F ully developed acute myocardial infarction was recognized at autopsy throughout the 19th and 20th century. Furthermore, many clinicians (eg, Osler) were excellent pathologists and often observed acute and healed myocardial infarcts (MI) in their patients after death. However, more often than not, the acute infarcts they observed did not show a thrombus in the coronary artery supplying the infarcted region of the heart. As a result, although the infarct was usually supplied by a particular coronary artery in the myocardium and the heart usually exhibited severe atherosclerotic coronary artery disease, there was enough variation from patient to patient so that the clinicians of this day were reluctant to attribute the myocardial necrosis to interruption of the blood supply.1 However, by 1880, several German experimentalists 2 had occluded major coronary arteries in the canine heart and found easily identifiable acute MI 24 hours later. However, these data failed to convince most of the experimentalists and the clinicians that human infarcts were caused by an interruption in coronary blood flow. Abstract: A selective history of the pathophysiological, structural, and metabolic changes found during an episode of severe myocardial ischemia in the canine heart is presented. The changes that cause ischemic injury to become irreversible are discussed in detail because these changes are the target of any successful therapy designed to prevent ischemic cell death. Of these, the disruption of the sarcolemma, an injury the development of which is accelerated in vivo by the contraction of viable tissue elsewhere in the heart traumatizing the ischemic area, plus the changes in high-energy phosphate and the total adenine nucleotide pool are considered to be the critical events leading to the development of irreversibility. The discovery of preconditioning with ischemia is discussed, together with a brief description of postconditioning. Finally, reperfusion injury is discussed in a summary fashion. The evidence for the fact that myocytes are salvaged by reperfusion is presented, as is the evidence that myocytes become unsalvageable by reperfusion as the duration of ischemia increases. The concept that some of the myocytes that die after successful reperfusion with arterial blood actually are killed by changes initiated by reperfusion, so-called lethal reperfusion injury, is attractive in that prevention of this change would lead to greater salvage; however, the prevalence of this phenomenon in clinical practice remains to be determined. of the thrombus restored arterial flow and reversed many of the clinical and electrocardiographic signs of on-going infarction. It seems likely that the explanation for the failure of the early workers to find a thrombus in hearts with a welldeveloped acute infarct was because of the action of endothelial fibrinolysins in the adjacent endothelium dissolving the thrombus that had caused the MI. Hence, although a coronary artery had to be obstructed to cause infarction, clots were observed irre...

show abstract

“…One mechanism for ischemic damage is the inhibition of mitochondrial ATP production due to lack of oxygen, which induces F 1 F 0 -ATPase running inversely to consume glycolytic ATP, leads to energy depravation (Rouslin et al 1986;Vuorinen et al 1995). Furthermore, overexpression of BCL-2 in the heart decreases the rate of ATP decline and reduces acidification, suggesting that BCL-2 may protect myocardium during ischemia by inhibiting consumption of glycolytic ATP generated by inversed F 1 F 0 -ATPase (Imahashi et al 2004).…”

Section: Apoptosis and Heart Diseasementioning

confidence: 99%

The Role of MCL-1 in the Heart: Gateway from Life to Death

Wang¹

View full text Add to dashboard Cite

Effects of oligomycin and acidosis on rates of ATP depletion in ischemic heart muscle

Cited by 61 publications

References 0 publications

Transgenic Expression of Bcl-2 Modulates Energy Metabolism, Prevents Cytosolic Acidification During Ischemia, and Reduces Ischemia/Reperfusion Injury

Transgenic Expression of Bcl-2 Modulates Energy Metabolism, Prevents Cytosolic Acidification During Ischemia, and Reduces Ischemia/Reperfusion Injury

Historical Perspective on the Pathology of Myocardial Ischemia/Reperfusion Injury

The Role of MCL-1 in the Heart: Gateway from Life to Death

Contact Info

Product

Resources

About