In vivo unaltered muscle protein synthesis in experimental chronic metabolic acidosis

Maniar, S.; Laouari, Denise; Déchaux, M; Motel, Véronique; Yvert, J. P.; Mathian, B.; Kleinknecht, C

doi:10.1038/ki.1994.472

Cited by 19 publications

(11 citation statements)

References 39 publications

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“…Only a few studies have investigated the effect of acidosis on individual tissues in vivo. Maniar et al (29) compared both muscle protein synthesis and degradation in a set of rats that were uremic and acidotic with those of similar pair-fed animals that were uremic but not acidotic because of receiving NaHCO 3 and with those of ad libitum-fed controls. They showed that rates of protein synthesis in muscle, measured in vivo with a flooding amount of L-[…”

Section: Discussionmentioning

confidence: 99%

“…However, when measurements were made in vitro in isolated muscles from acidotic animals, some studies detected an inhibition of protein synthesis by acidosis (20,25), while others showed no effect (32,33). Similarly, whereas some studies investigating the in vivo effect of acidosis on muscle protein synthesis have failed to detect a response (13,29), others have shown a clear inhibitory effect of acidosis on muscle protein and albumin synthesis rates (3,23).…”

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confidence: 99%

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Acute metabolic acidosis inhibits muscle protein synthesis in rats

Caso¹,

Garlick²,

Casella³

et al. 2004

American Journal of Physiology-Endocrinology and Metabolism

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In this study, we investigated the effect of acute metabolic acidosis on tissue protein synthesis. Groups of rats were made acidotic with intragastric administration of NH4Cl (20 mmol/kg body wt every 12 h for 24 h) or given equimolar amounts of NaCl (controls). Protein synthesis in skeletal muscle and a variety of different tissues, including lymphocytes, was measured after 24 h by injection of l-[2H5]phenylalanine (150 μmol/100 g body wt, 40 moles percent). Results show that acute acidosis inhibits protein synthesis in skeletal muscle (−29% in gastrocnemius, −23% in plantaris, and −17% in soleus muscles, P < 0.01) but does not affect protein synthesis in heart, liver, gut, kidney, and spleen. Protein synthesis in lymphocytes is also reduced by acidosis (−8%, P < 0.05). In a separate experiment, protein synthesis was also measured in acidotic and control rats by a constant infusion of l-[2H5]phenylalanine (1 μmol·100 g body wt−1·h−1). The results confirm the earlier findings showing an inhibition of protein synthesis in gastrocnemius (−28%, P < 0.01) and plantaris (−19%, P < 0.01) muscles but no effect on heart and liver by acidosis. Similar results were also observed using a different model of acute metabolic acidosis, in which rats were given a cation exchange resin in the H+ (acidotic) or the Na+ (controls) form. In conclusion, this study demonstrates that acute metabolic acidosis for 24 h depresses protein synthesis in skeletal muscle and lymphocytes but does not alter protein synthesis in visceral tissues. Inhibition of muscle protein synthesis might be another mechanism contributing to the loss of muscle tissue observed in acidosis.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Acute metabolic acidosis inhibits muscle protein synthesis in rats

Caso¹,

Garlick²,

Casella³

et al. 2004

American Journal of Physiology-Endocrinology and Metabolism

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“…In vivo protein synthesis may be normal [7] or even increased [4] in response to metabolic acidosis but the duration of the acidosis may be relevant, since protein synthesis during starvation may rise again after its initial fall [22]. In prolonged starvation, metabolic acidosis (ketoacidosis) may contribute to the observed protein wasting since correction of the ketoacidosis with bicarbonate supplements rectifies the increased nitrogen excretion [23], but this is unlikely to be the full explanation for the similarities since ketoacidosis develops too slowly [1] to account for the early changes in protein synthesis and degradation during starvation.…”

Section: Discussionmentioning

confidence: 99%

“…Even though it is well established that uraemic metabolic acidosis stimulates protein degradation and is a major contributor to skeletal muscle wasting in chronic Bevington/Poulter/Brown/Walls renal failure [4][5][6], the accompanying effects of metabolic acidosis on protein synthesis are much less clear. Different studies have detected an increase [4], no effect [7] or a possible decrease [8] in vivo in response to metabolic acidosis. A possible explanation for these disparities is that acidosis induces a number of conflicting effects on protein synthesis, with humoral [3,9] or long-term adaptive responses being superimposed on the direct effects of low pH or low bicarbonate on the skeletal muscle cells.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Protein Synthesis by Acid in L6 Skeletal Muscle Cells: Analogies with the Acute Starvation Response

Bevington¹,

Poulter²,

Brown³

et al. 1998

Mineral Electrolyte Metab

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Impaired protein synthesis (PS) occurs in skeletal muscle during acute starvation. Even though it is well established that uraemic metabolic acidosis (MA) stimulates protein degradation (PD) and is a major contributor to skeletal muscle wasting in chronic renal failure, the accompanying effects of MA on PS are much less clear. Previous work has shown that, in cultured L6 skeletal muscle cells, PD and leucine oxidation are stimulated by acid. The aim of the present study was to determine whether acid (like acute starvation) can also inhibit PS. PS (¹⁴C-phenylalanine incorporation) was measured in L6 cells in MEM + 2% serum at acid pH (7.1) or control pH (7.5). After 24 h, acid inhibited PS (7.7 ± 0.2 vs. 8.9 ± 0.1 nmol Phe/4 h/35-mm culture well in controls, p = 0.01) and this was maintained at 72 h. In vitro this could arise because acid only inhibits the rapid PS occurring in dividing cells. However, when division was abolished with 10^–5 mol/l cytosine arabinoside, PS inhibition by acid still occurred (6.9 ± 0.1 vs. 8.3 ± 0.2 at control pH, p < 0.05). Acid also had no effect on the specific radioactivity of cellular phenylalanine, suggesting that the impaired PS was not a consequence of inadequate labelling of this pool. Elevated PD and impaired PS together led to loss of 7% of the total protein in only 28 h (–21 ± 3 µg/well, p = 0.004). This combination of impaired PS with increased PD and increased leucine oxidation in response to acid resembles the response of skeletal muscle to acute starvation. These superficial similarities between the starvation state and MA suggest that fundamental metabolic signals may occur which are common to both states.

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“…In addition, a depression in muscle protein synthesis was observed after 2 days of metabolic acidosis in humans [18] and after 1 day in rats [19, 20]. However, prior studies had failed to detect a response in protein synthesis [21, 22]. …”

Section: Introductionmentioning

confidence: 99%

Does Increasing Blood pH Stimulate Protein Synthesis in Dialysis Patients?

et al. 2009

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Background: Although the mechanism of muscle wasting in end-stage renal disease is not fully understood, there is increasing evidence that acidosis induces muscle protein degradation and could therefore contribute to the loss of muscle protein stores of patients on hemodialysis, a prototypical state of chronic metabolic acidosis (CMA). Because body protein mass is controlled by the balance between synthesis and degradation, protein loss can occur as result of either increased breakdown, impaired synthesis, or both. Correction of acidosis may therefore help to maintain muscle mass and improve the health of patients with CMA. We evaluated whether alkalizing patients on hemodialysis might have a positive effect on protein synthesis and on nutritional parameters. Methods: Eight chronic hemodialysis patients were treated daily with oral sodium bicarbonate (NaHCO₃) supplementation for 10–14 days, yielding a pre-dialytic plasma bicarbonate concentration of 28.6 ±1.6 mmol/l. The fractional synthesis rates (FSR) of muscle protein and albumin were obtained by the L-[²H₅ring]phenylalanine flooding technique. Results: Oral NaHCO₃supplementation induced a significant increase in serum bicarbonate (21.5 ± 3.4 vs. 28.6 ± 1.6 mmol/l; p = 0.018) and blood pH (7.41 vs. 7.46; p = 0.041). The FSR of muscle protein and the FSR of albumin did not change significantly (muscle protein: 2.1 ± 0.2 vs. 2.0 ± 0.5% per day, p = 0.39; albumin: 8.3 ± 2.2 vs. 8.6 ± 2.5% per day, p = 0.31). Plasma concentrations of insulin-like growth factor 1 decreased significantly (33.4 ± 21.3 vs. 25.4 ± 12.3 nmol/l; p = 0.028), whereas thyroid-stimulating hormone, free thyroxin and free triiodothyronine did not change significantly and nutritional parameters showed no improvement. Conclusion: In contrast to other findings, raising the blood pH of dialysis patients was not associated with a positive effect on albumin and muscle protein synthesis, or nutritional and endocrinal parameters.

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In vivo unaltered muscle protein synthesis in experimental chronic metabolic acidosis

Cited by 19 publications

References 39 publications

Acute metabolic acidosis inhibits muscle protein synthesis in rats

Acute metabolic acidosis inhibits muscle protein synthesis in rats

Inhibition of Protein Synthesis by Acid in L6 Skeletal Muscle Cells: Analogies with the Acute Starvation Response

Does Increasing Blood pH Stimulate Protein Synthesis in Dialysis Patients?

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