Response of protein synthesis to hypercapnia in rats: independent effects of acidosis and hypothermia

Caso, Giuseppe; Garlick, Barbara A.; Casella, George; Sasvary, Dawn; Garlick, Peter J.

doi:10.1016/j.metabol.2005.01.026

Cited by 5 publications

(5 citation statements)

References 32 publications

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“…Chronic hypercapnia elicits disturbances in acid-base homeostasis, and indeed, prolonged hypercapnia of levels comparable to those used in our experiments induces chronic acidosis in neonatal and adult mammals (16,38). Although the extent of renal compensation and altered metabolism may contribute to the compensatory changes in response to respiratory acidosis, the major factor in the readjustment of steadystate pH i homeostasis is the activity and level of expression of plasma membrane acid-base transporters (12).…”

Section: Discussionmentioning

confidence: 60%

“…The more widespread response to elevated CO 2 in newborn mice compared with adults may reflect several developmental differences in pH homeostasis: 1) maturation of mouse kidney occurs during the first 2 wk postnatally, where there is a coordinated increase in proteins that are involved in bicarbonate reabsorption and acid excretion both in the proximal tubule and the intercalated cells of the collecting duct (11). This results in lower levels of neonatal plasma bicarbonate and decreased ability to excrete acid loads compared with adults; and 2) hypercapnia in adults decreases production of metabolic acid equivalents (reflected by lowered arterial lactate levels), by induction of hypothermia and reduction in metabolism, oxygen consumption, and protein synthesis (16,41). Adult mice may rely on these mechanisms to counteract the hypercapnia-induced acidosis, thus diminishing the need to alter expression of acid-base transporter proteins.…”

Section: Discussionmentioning

confidence: 99%

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Effect of chronic elevated carbon dioxide on the expression of acid-base transporters in the neonatal and adult mouse

Kanaan

Douglas

Alper

et al. 2007

American Journal of Physiology-Regulatory, Integrative and Comp

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Several pulmonary and neurological conditions, both in the newborn and adult, result in hypercapnia. This leads to disturbances in normal pH homeostasis. Most mammalian cells maintain tight control of intracellular pH (pH(i)) using a group of transmembrane proteins that specialize in acid-base transport. These acid-base transporters are important in adjusting pH(i) during acidosis arising from hypoventilation. We hypothesized that exposure to chronic hypercapnia induces changes in the expression of acid-base transporters. Neonatal and adult CD-1 mice were exposed to either 8% or 12% CO(2) for 2 wk. We used Western blot analysis of membrane protein fractions from heart, kidney, and various brain regions to study the response of specific acid-base transporters to CO(2). Chronic CO(2) increased the expression of the sodium hydrogen exchanger 1 (NHE1) and electroneutral sodium bicarbonate cotransporter (NBCn1) in the cerebral cortex, heart, and kidney of neonatal but not adult mice. CO(2) increased the expression of electrogenic NBC (NBCe1) in the neonatal but not the adult mouse heart and kidney. Hypercapnia decreased the expression of anion exchanger 3 (AE3) in both the neonatal and adult brain but increased AE3 expression in the neonatal heart. We conclude that: 1) chronic hypercapnia increases the expression of the acid extruders NHE1, NBCe1 and NBCn1 and decreases the expression of the acid loader AE3, possibly improving the capacity of the cell to maintain pH(i) in the face of acidosis; and 2) the heterogeneous response of tissues to hypercapnia depends on the level of CO(2) and development.

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Section: Discussionmentioning

confidence: 60%

Section: Discussionmentioning

confidence: 99%

Effect of chronic elevated carbon dioxide on the expression of acid-base transporters in the neonatal and adult mouse

Kanaan

Douglas

Alper

et al. 2007

American Journal of Physiology-Regulatory, Integrative and Comp

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“…However, muscle K s in the Ane-AA group remained lower than in the Nor-Sal group, implying that some systemic alteration during anesthesia limits the effect of insulin on muscle protein synthesis. As a factor, the decline in body temperature itself might play a significant role in lowering the K s in the Ane-AA group, as is suggested by the finding that a drop of 2°C in body temperature results in an ϳ20% inhibition of K s in skeletal muscle and liver of rats (8). The fall in metabolic rate caused by the administration of anesthetics may be also relevant to the negative effect on the protein synthesis due to the fall in metabolic rate, because the treatment with anesthetics depresses metabolic rate 20 to 30% (38) and the amount of oxygen consumption correlates with the K s (21).…”

Section: Discussionmentioning

confidence: 93%

Intravenous administration of amino acids during anesthesia stimulates muscle protein synthesis and heat accumulation in the body

Yamaoka¹,

Doi²,

Nakayama³

et al. 2006

American Journal of Physiology-Endocrinology and Metabolism

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The present study was conducted to determine the contribution of muscle protein synthesis to the prevention of anesthesia-induced hypothermia by intravenous administration of an amino acid (AA) mixture. We examined the changes of intraperitoneal temperature (Tcore) and the rates of protein synthesis (K(s)) and the phosphorylation states of translation initiation regulators and their upstream signaling components in skeletal muscle in conscious (Nor) or propofol-anesthetized (Ane) rats after a 3-h intravenous administration of a balanced AA mixture or saline (Sal). Compared with Sal administration, the AA mixture administration markedly attenuated the decrease in Tcore in rats during anesthesia, whereas Tcore in the Nor-AA group became slightly elevated during treatment. Stimulation of muscle protein synthesis resulting from AA administration was observed in each case, although K(s) remained lower in the Ane-AA group than in the Nor-Sal group. AA administration during anesthesia significantly increased insulin concentrations to levels approximately 6-fold greater than in the Nor-AA group and enhanced phosphorylation of eukaryotic initiation factor 4E-binding protein-1 (4E-BP1) and ribosomal protein S6 protein kinase relative to all other groups and treatments. The alterations in the Ane-AA group were accompanied by hyperphosphorylation of protein kinase B and the mammalian target of rapamycin (mTOR). These results suggest that administration of an AA mixture during anesthesia stimulates muscle protein synthesis via insulin-mTOR-dependent activation of translation initiation regulators caused by markedly elevated insulin and, thereby, facilitates thermal accumulation in the body.

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“…Both pH and lactate normalized rapidly following exercise (although they were still significantly different from basal 1 h post‐exercise). Recent work in rodent muscle has shown 24 h of acute metabolic acidosis (Caso et al 2004) and 1 h of respiratory acidosis (Caso et al 2005) significantly decrease skeletal muscle protein synthesis. It has also been reported that 48 h of metabolic acidosis in humans suppresses muscle protein synthesis (Kleger et al 2001).…”

Section: Discussionmentioning

confidence: 99%

Resistance exercise increases AMPK activity and reduces 4E‐BP1 phosphorylation and protein synthesis in human skeletal muscle

Dreyer

Fujita²,

Cadenas³

et al. 2006

The Journal of Physiology

468

472

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Resistance exercise is a potent stimulator of muscle protein synthesis and muscle cell growth, with the increase in protein synthesis being detected within 2-3 h post-exercise and remaining elevated for up to 48 h. However, during exercise, muscle protein synthesis is inhibited. An increase in AMP-activated protein kinase (AMPK) activity has recently been shown to decrease mammalian target of rapamycin (mTOR) signalling to key regulators of translation initiation. We hypothesized that the cellular mechanism for the inhibition of muscle protein synthesis during an acute bout of resistance exercise in humans would be associated with an activation of AMPK and an inhibition of downstream components of the mTOR pathway (4E-BP1 and S6K1). We studied 11 subjects (seven men, four women) before, during, and for 2 h following a bout of resistance exercise. Muscle biopsy specimens were collected at each time point from the vastus lateralis. We utilized immunoprecipitation and immunoblotting methods to measure muscle AMPKα2 activity, and mTOR-associated upstream and downstream signalling proteins, and stable isotope techniques to measure muscle fractional protein synthetic rate (FSR). AMPKα2 activity (pmol min −1 (mg protein) −1 ) at baseline was 1.7 ± 0.3, increased immediately post-exercise (3.0 ± 0.6), and remained elevated at 1 h post-exercise (P < 0.05). Muscle FSR decreased during exercise and was significantly increased at 1 and 2 h post-exercise (P < 0.05). Phosphorylation of 4E-BP1 at Thr37/46 was significantly reduced immediately post-exercise (P < 0.05). We conclude that AMPK activation and a reduced phosphorylation of 4E-BP1 may contribute to the inhibition of muscle protein synthesis during resistance exercise. However, by 1-2 h post-exercise, muscle protein synthesis increased in association with an activation of protein kinase B, mTOR, S6K1 and eEF2.

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Response of protein synthesis to hypercapnia in rats: independent effects of acidosis and hypothermia

Cited by 5 publications

References 32 publications

Effect of chronic elevated carbon dioxide on the expression of acid-base transporters in the neonatal and adult mouse

Effect of chronic elevated carbon dioxide on the expression of acid-base transporters in the neonatal and adult mouse

Intravenous administration of amino acids during anesthesia stimulates muscle protein synthesis and heat accumulation in the body

Resistance exercise increases AMPK activity and reduces 4E‐BP1 phosphorylation and protein synthesis in human skeletal muscle

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