Chronic hypoxemia increases myocardial cytochrome oxidase

Piel, David; Khan, Azeem; Waibel, Robert; Birbach, Mariusz; Cohen, Meryl S.; Spray, Thomas L.; Deutschman, Clifford S.; Gaynor, J. William; Levy, Richard J.

doi:10.1016/j.jtcvs.2005.06.030

Cited by 12 publications

(18 citation statements)

References 17 publications

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“…As previously described, cardiac ventricles were harvested and homogenized in ice-cold H medium (70 mM sucrose, 220 mM mannitol, 2.5 mM 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid, pH 7.4, and 2 mM EDTA) (8,19). The homogenate was spun at 1,500g for 10 min at 4°C.…”

Section: Mitochondrial Isolationmentioning

confidence: 99%

“…Pellets were resuspended in H medium and centrifuged again at 10,000g for 10 min at 4°C. Pellets were again resuspended in H medium, and mitochondrial protein concentration was determined using the method of Lowry (8,19,20).…”

Section: Mitochondrial Isolationmentioning

confidence: 99%

“…Cytochrome oxidase kinetics were assayed by the method of Smith, in which the rate of oxidation of ferrocytochrome c was measured by following the decrease in absorbance at 550 nm (8,19,20). Assays were executed in a 1-mL reaction volume containing 50 mM PO 4 -2 (pH 7.0), 2% lauryl maltoside, and 1 μg of mitochondrial protein.…”

Section: Ccox Steady-state Kineticsmentioning

confidence: 99%

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Exogenous Cytochrome C Restores Myocardial Cytochrome Oxidase Activity Into the Late Phase of Sepsis

Piel

Deutschman

Levy

2008

Shock

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Mitochondrial dysfunction is thought to play a role in the pathogenesis of a variety of disease states, including sepsis. An acquired defect in oxidative phosphorylation potentially causes sepsisinduced organ dysfunction. Cytochrome oxidase (CcOX), the terminal oxidase of the respiratory chain, is competitively inhibited early in sepsis and progresses, becoming noncompetitive during the late phase. We have previously demonstrated that exogenous cytochrome c can overcome myocardial CcOX competitive inhibition and improve cardiac function during murine sepsis at the 24-h point. Here, we evaluate the effect of exogenous cytochrome c on CcOX activity and survival in mice at the later time points. Exogenous cytochrome c (800 μg) or saline was intravenously injected 24 h after cecal ligation and puncture (CLP) or sham operation. Steady-state mitochondrial cytochrome c levels and heme c content increased significantly 48 h post-CLP and remained elevated at 72 h in cytochrome c-injected mice compared with saline injection. Cecal ligation and puncture inhibited CcOX at 48 h in saline-injected mice. However, cytochrome c injection abrogated this inhibition and restored CcOX kinetic activity to sham values at 48 h. Survival after CLP to 96 h after cytochrome c injection approached 50% compared with only 15% after saline injection. Thus, a single injection of exogenous cytochrome c 24 h post-CLP repletes mitochondrial substrate levels for up to 72 h, restores myocardial COX activity, and significantly improves survival.

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Section: Mitochondrial Isolationmentioning

confidence: 99%

Section: Mitochondrial Isolationmentioning

confidence: 99%

Section: Ccox Steady-state Kineticsmentioning

confidence: 99%

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Exogenous Cytochrome C Restores Myocardial Cytochrome Oxidase Activity Into the Late Phase of Sepsis

Piel

Deutschman

Levy

2008

Shock

Self Cite

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“…Previously described models include direct anastomosis between the inferior vena cava and the right lower-lobe pulmonary vein [10] or LA [11], direct LA-PA anastomosis with PA banding [12], atrial septostomy with PA banding [1][2][3][4][5][6][7], and interposition grafting between the LA and PA [13][14][15]. We prefer right-to-left shunting with a PA-to-LA synthetic graft.…”

Section: Discussionmentioning

confidence: 99%

“…Swine models based on pulmonary artery (PA)-left atrial (LA) shunts have been described [1][2][3][4][5][6][7]. However, hypercoagulability [8,9] promotes clotting in areas of stasis or contact with foreign material, which, along with other perioperative factors, renders such models potentially unusable and affords high mortality rates.…”

Section: Introductionmentioning

confidence: 99%

Developing and Optimizing a Chronic Cyanotic Swine Model

Gerrah

Cabreriza

Rusanov

et al. 2011

Journal of Surgical Research

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Nitrite activates AMP kinase to stimulate mitochondrial biogenesis independent of soluble guanylate cyclase

Wang

Geary

et al. 2012

Free Radical Biology and Medicine

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Nitrite, a dietary constituent and endogenous signaling molecule, mediates a number of physiological responses including modulation of ischemia/reperfusion injury, glucose tolerance and vascular remodeling. While the exact molecular mechanisms underlying nitrite’s actions are unknown, current paradigm suggests that these effects depend on the hypoxic reduction of nitrite to nitric oxide (NO). Mitochondrial biogenesis is a fundamental mechanism of cellular adaptation and repair. However, the effect of nitrite on mitochondrial number has not been explored. Herein, we report that nitrite stimulates mitochondrial biogenesis through a mechanism distinct from NO. We demonstrate that nitrite significantly increases cellular mitochondrial number by augmenting the activity of adenylate kinase, resulting in AMP kinase phosphorylation, downstream activation of sirtuin-1, and de-acetylation of PGC1, the master regulator of mitochondrial biogenesis. Unlike NO, nitrite-mediated biogenesis does not require the activation of soluble guanylate cyclase and results in the synthesis of more functionally efficient mitochondria. Further, we provide evidence that nitrite mediates biogenesis in vivo. In a rat model of carotid injury, two weeks of continuous oral nitrite treatment post-injury prevents the hyperproliferative response of smooth muscle cells. This protection is accompanied by a nitrite-dependent upregulation of PGC1 and increased mitochondrial number in the injured artery. These data are the first to demonstrate that nitrite mediates differential signaling than NO. They show that nitrite is a versatile regulator of mitochondrial function and number both in vivo and in vitro, and suggest that nitrite-mediated biogenesis may play a protective role in the setting of vascular injury.

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Chronic hypoxemia increases myocardial cytochrome oxidase

Abstract: Chronic hypoxemia increases cytochrome oxidase I message, protein expression, and activity. The increase in kinetics was due to increased enzyme content and catalytic activity. This is a possible adaptive mechanism that might preserve organ function during chronic hypoxemia.

Cited by 12 publications

References 17 publications

Exogenous Cytochrome C Restores Myocardial Cytochrome Oxidase Activity Into the Late Phase of Sepsis

Exogenous Cytochrome C Restores Myocardial Cytochrome Oxidase Activity Into the Late Phase of Sepsis

Developing and Optimizing a Chronic Cyanotic Swine Model

Nitrite activates AMP kinase to stimulate mitochondrial biogenesis independent of soluble guanylate cyclase

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