Determination of cytosolic ADP and AMP concentrations and the free energy of ATP hydrolysis in human muscle and brain tissues with <sup>31</sup>P NMR spectroscopy

Roth, Klaus; Weiner, Michael W.

doi:10.1002/mrm.1910220258

Cited by 67 publications

(52 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The binding of a phosphorothioate oligodeoxyribonucleotide to albumin increased with the number of phosphorothioate linkages (16). The binding of dA 36 to the g5p protein increases more than 300-fold after substitution of sulfur for oxygen in an oligonucleotide (29).…”

Section: Discussionmentioning

confidence: 99%

“…Inside the cell, more than half the ADP is bound to proteins (3,4,28). The free [ADP] from various cell types is not directly known but has been estimated to be 6 -90 M (3,36,45). The failure to detect the ADP by 31 P-NMR argues for the real concentration to be in the low end of that range (3,36).…”

Section: Discussionmentioning

confidence: 99%

“…The free [ADP] from various cell types is not directly known but has been estimated to be 6 -90 M (3,36,45). The failure to detect the ADP by 31 P-NMR argues for the real concentration to be in the low end of that range (3,36). In any event, this range is within the concentration range at which G3139-induced MOM permeability reduction limits the rate of ADP phosphorylation.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Phosphorothioate oligonucleotides reduce mitochondrial outer membrane permeability to ADP

Tan¹,

Lai²,

Miller³

et al. 2007

American Journal of Physiology-Cell Physiology

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Phosphorothioate oligonucleotides reduce mitochondrial outer membrane permeability to ADP

Tan¹,

Lai²,

Miller³

et al. 2007

American Journal of Physiology-Cell Physiology

View full text Add to dashboard Cite

show abstract

“…The permeability changes induced by these dinucleotides result in large differences in the concentration of ADP between the cytosol and the intermembrane space (Fig. 4B) especially at the low, physiologically relevant concentrations of ADP (micromolar level; Brindle et al (1989), Roth and Weiner (1991), and Wan et al (1993)). Such dynamic compartmentation has been reported in particular physiological states where estimates of these changes can be made (Gellerich et al, 1987).…”

Section: Table I Nad(p)h Increases the Voltage Dependence Of Vdacmentioning

confidence: 99%

The Role of Pyridine Dinucleotides in Regulating the Permeability of the Mitochondrial Outer Membrane

Lee¹,

Colombini

1996

Journal of Biological Chemistry

View full text Add to dashboard Cite

Both NADH and NADPH reduce the permeability of the mitochondrial outer membrane to ADP. This is specific for the outer membrane and uncorrelated with the respiratory control ratio. This could result in a 7-fold difference between the concentration of ADP in the intermembrane space and that in the external environment (at 5 M ADP). In both cases the permeability declines by a factor of 5, but NADH is more potent: K D ‫؍‬ 86 M for NADH versus 580 M for NADPH. The lower apparent affinity for NADPH is partly explained by Mg 2؉ -NADPH being the active species, and under our conditions only 30% of the NADPH is in this form. The corrected K D is 184 M. Free NADH has the same charge as the Mg 2؉ -NADPH complex, and thus both likely bind to the same site. The ability of NADH and NADPH to induce the closure of reconstituted VDAC channels is consistent with VDAC being the main pathway for metabolite flow across the outer membrane. Oncotic pressure, effective at inducing VDAC closure, also decreases the outer membrane permeability. Thus, in the presence of cytosolic colloidal osmotic pressure NAD(P)H may inhibit mitochondrial catabolic pathways and divert reducing equivalents to anabolic pathways.

show abstract

“…Absolute amounts of phosphorylated compounds were expressed relative to a resting ATP concentration determined in vitro using a bioluminescence-based method (see below), and intracellular pH was calculated from the chemical shift of the P i signal relative to PCr (3). ADP concentration was calculated from [PCr], [ATP], and pH, considering the equilibrium constant (K ϭ 1.67 10 9 M Ϫ1 ) of the creatine kinase (CK) reaction (53). VPCrstim (the initial rate of PCr degradation at the start of the fatiguing exercise, in mM/min) was calculated as the product of kstim (the pseudo-first-order rate constant of PCr degradation) and [PCr]cons (the amount of PCr consumed at the end of the exercise).…”

Section: Noninvasive Investigation Of Gastrocnemius Muscle Function Amentioning

confidence: 99%

Mitochondrial impairment induced by postnatal ActRIIB blockade does not alter function and energy status in exercising mouse glycolytic muscle in vivo

Béchir

Pecchi

Relizani

et al. 2016

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

-Because it leads to a rapid and massive muscle hypertrophy, postnatal blockade of the activin type IIB receptor (ActRIIB) is a promising therapeutic strategy for counteracting muscle wasting. However, the functional consequences remain very poorly documented in vivo. Here, we have investigated the impact of 8-wk ActRIIB blockade with soluble receptor (sActRIIB-Fc) on gastrocnemius muscle anatomy, energy metabolism, and force-generating capacity in wild-type mice, using totally noninvasive magnetic resonance imaging (MRI) and dynamic 31 P-MRS. Compared with vehicle (PBS) control, sActRIIB-Fc treatment resulted in a dramatic increase in body weight (ϩ29%) and muscle volume (ϩ58%) calculated from hindlimb MR imaging, but did not alter fiber type distribution determined via myosin heavy chain isoform analysis. In resting muscle, sActRIIB-Fc treatment induced acidosis and PCr depletion, thereby suggesting reduced tissue oxygenation. During an in vivo fatiguing exercise (6-min repeated maximal isometric contraction electrically induced at 1.7 Hz), maximal and total absolute forces were larger in sActRIIB-Fc treated animals (ϩ26 and ϩ12%, respectively), whereas specific force and fatigue resistance were lower (Ϫ30 and Ϫ37%, respectively). Treatment with sActRIIB-Fc further decreased the maximal rate of oxidative ATP synthesis (Ϫ42%) and the oxidative capacity (Ϫ34%), but did not alter the bioenergetics status in contracting muscle. Our findings demonstrate in vivo that sActRIIB-Fc treatment increases absolute force-generating capacity and reduces mitochondrial function in glycolytic gastrocnemius muscle, but this reduction does not compromise energy status during sustained activity. Overall, these data support the clinical interest of postnatal ActRIIB blockade. skeletal muscle hypertrophy; activin type IIB receptor; myostatin; force; fatigue ACTIVIN TYPE IIB RECEPTOR (ActRIIB) is a transmembrane serinethreonine kinase receptor highly expressed in mammalian skeletal muscle. It mediates signaling for myostatin (GDF8) and other members of the transforming growth factor-␤ family that are involved in the negative regulation of skeletal muscle development (16,37). Disruption of the ActRIIB signaling pathway leads to a rapid and massive increase in muscle mass resulting from fiber hypertrophy with increased myofiber protein synthesis (10, 58). In that context, several pharmacological approaches based on the postnatal ActRIIB signaling blockade have been considered for counteracting muscle wasting commonly associated to aging, neuromuscular disorders and various catabolic diseases (17,33,38). These approaches mainly include the systemic delivery of neutralizing antibodies against ActRIIB or myostatin (31, 36), and injection of a soluble recombinant form of ActRIIB (sActRIIB-Fc), which acts as a decoy receptor disrupting the interaction of endogenous ActRIIB receptor with its ligands (5,38,44).Although ActRIIB signaling blockade has been already tested in patients (30, 57) and animal models (10,44,47) suffering from dystrophi...

show abstract

Determination of cytosolic ADP and AMP concentrations and the free energy of ATP hydrolysis in human muscle and brain tissues with ³¹P NMR spectroscopy

Cited by 67 publications

References 26 publications

Phosphorothioate oligonucleotides reduce mitochondrial outer membrane permeability to ADP

Phosphorothioate oligonucleotides reduce mitochondrial outer membrane permeability to ADP

The Role of Pyridine Dinucleotides in Regulating the Permeability of the Mitochondrial Outer Membrane

Mitochondrial impairment induced by postnatal ActRIIB blockade does not alter function and energy status in exercising mouse glycolytic muscle in vivo

Contact Info

Product

Resources

About

Determination of cytosolic ADP and AMP concentrations and the free energy of ATP hydrolysis in human muscle and brain tissues with 31P NMR spectroscopy

Cited by 67 publications

References 26 publications

Phosphorothioate oligonucleotides reduce mitochondrial outer membrane permeability to ADP

Phosphorothioate oligonucleotides reduce mitochondrial outer membrane permeability to ADP

The Role of Pyridine Dinucleotides in Regulating the Permeability of the Mitochondrial Outer Membrane

Mitochondrial impairment induced by postnatal ActRIIB blockade does not alter function and energy status in exercising mouse glycolytic muscle in vivo

Contact Info

Product

Resources

About

Determination of cytosolic ADP and AMP concentrations and the free energy of ATP hydrolysis in human muscle and brain tissues with ³¹P NMR spectroscopy