Gender Comparisons of Control of Breathing and Metabolism in Conscious Mice Exposed to Cold

Schlenker, Evelyn H.; Hansen, Susan N.; Pfaff, Donald W.

doi:10.1159/000067580

Cited by 7 publications

(3 citation statements)

References 43 publications

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“…Although Swiss-Webster mice have been used in studies concerned with the effects of 2 min episodes of HX and HC challenges on ventilatory parameters (Schenkler et al, 2002) and the effects of 5 min episodes of hypoxia-induced gasping (Jacobi and Thach, 1989), no studies have addressed the relationships between ventilatory performance and level of disordered breathing at rest, during HX or HC challenges, and upon return to room-air. Our findings comparing the three mouse strains was that resting Rinx was not necessarily a function of the magnitude of resting f R since Swiss-Webster (and in particular B6AF1 mice) had higher f R at rest than C57BL6 mice but substantially lower Rinx values than the C57BL6 mice.…”

Section: Discussionmentioning

confidence: 99%

Enhanced non-eupneic breathing following hypoxic, hypercapnic or hypoxic–hypercapnic gas challenges in conscious mice

Getsy¹,

Davis²,

Coffee³

et al. 2014

Respiratory Physiology & Neurobiology

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C57BL6 mice display non-eupneic breathing and spontaneous apneas during wakefulness and sleep as well as markedly disordered breathing following cessation of a hypoxic challenge. We examined whether (1) C57BL6 mice display marked non-eupneic breathing following hypercapnic or hypoxic-hypercapnic challenges, and (2) compared the post-hypoxia changes in non-eupneic breathing of C57BL6 mice to those of B6AF1 (57BL6 dam × A/J sire) and Swiss-Webster mice, which display different ventilatory responses than C57BL6 mice. C57BL6 mice displayed marked increases in respiratory frequency and non-eupneic breathing upon return to room-air after hypoxic (10% O2, 90% N2), hypercapnic (5% CO2, 21% O2, 74% N2) and hypoxic-hypercapnic (10% O2, 5% CO2, 85% N2) challenges. B6AF1 mice displayed less tachypnea and reduced non-eupneic breathing post-hypoxia, whereas Swiss-Webster mice displayed robust tachypnea with minimal increases in non-eupneic breathing post-hypoxia. These studies demonstrate that non-eupneic breathing increases after physiologically-relevant hypoxic-hypercapnic challenge in C57BL6 mice and suggest that further studies with these and B6AF1 and Swiss-Webster mice will help define the genetics of non-eupneic breathing.

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Section: Discussionmentioning

confidence: 99%

Enhanced non-eupneic breathing following hypoxic, hypercapnic or hypoxic–hypercapnic gas challenges in conscious mice

Getsy¹,

Davis²,

Coffee³

et al. 2014

Respiratory Physiology & Neurobiology

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show abstract

“…These results suggested that Sirt2 may inhibit degradation of PKM2 by the ubiquitin-proteasome pathway. Because different forms of ubiquitin chains play different roles in regulating protein function [ 44 , 45 ], we transfected Flag-PKM2 expression plasmids into HEK293T cells together with a ubiquitin plasmid containing only a single lysine residue. We found that PKM2 had the highest level of ubiquitination at K48 in the CoCl2 construct model (Fig.…”

Section: Resultsmentioning

confidence: 99%

The role of NAD-dependent deacetylase sirtuin-2 in liver metabolic stress through regulating pyruvate kinase M2 ubiquitination

Guo,

Nie,

et al. 2024

J Transl Med

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NAD-dependent deacetylase Sirt2 is involved in mammalian metabolic activities, matching energy demand with energy production and expenditure, and is relevant to a variety of metabolic diseases. Here, we constructed Sirt2 knockout and adeno-associated virus overexpression mice and found that deletion of hepatic Sirt2 accelerated primary obesity and insulin resistance in mice with concomitant hepatic metabolic dysfunction. However, the key targets of Sirt2 are unknown. We identified the M2 isoform of pyruvate kinase (PKM2) as a key Sirt2 target involved in glycolysis in metabolic stress. Through yeast two-hybrid and mass spectrometry combined with multi-omics analysis, we identified candidate acetylation modification targets of Sirt2 on PKM2 lysine 135 (K135). The Sirt2-mediated deacetylation-ubiquitination switch of PKM2 regulated the development of glycolysis. Here, we found that Sirt2 deficiency led to impaired glucose tolerance and insulin resistance and induced primary obesity. Sirt2 severely disrupted liver function in mice under metabolic stress, exacerbated the metabolic burden on the liver, and affected glucose metabolism. Sirt2 underwent acetylation modification of lysine 135 of PKM2 through a histidine 187 enzyme active site-dependent effect and reduced ubiquitination of the K48 ubiquitin chain of PKM2. Our findings reveal that the hepatic glucose metabolism links nutrient state to whole-body energetics through the rhythmic regulation of Sirt2.

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“…We further explored the role of Sirt2 in the deacetylation function of PKM2. Hypoxia has been reported to induce metabolic reprogramming of cells [43]. Therefore, we treated AML12 cells using the hypoxia mimetic cobalt chloride (CoCl2) (30 µmol) to generate a glucose metabolic reprogramming model.…”

Section: Inhibition Of Sirt2 Promotes Expression Of Pkm2 and Increase...mentioning

confidence: 99%

The role of NAD-dependent deacetylase sirtuin-2 in liver metabolic stress through regulating Pyruvate kinase M2 ubiquitination

Guo,

Nie,

et al. 2024

Preprint

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NAD-dependent deacetylase Sirt2 is involved in mammalian metabolic activities, matching energy demand with energy production and expenditure, and is relevant to a variety of metabolic diseases. Here, we constructed Sirt2 knockout and adeno-associated virus overexpression mice and found that deletion of hepatic Sirt2 accelerated primary obesity and insulin resistance in mice with concomitant hepatic metabolic dysfunction. However, the key targets of Sirt2 are unknown. We identified the M2 isoform of pyruvate kinase (PKM2) as a key Sirt2 target involved in glycolysis in metabolic stress. Through yeast two-hybrid and mass spectrometry combined with multi-omics analysis, we identified candidate acetylation modification targets of SIRT2 on PKM2 lysine 135 (K135). The Sirt2-mediated deacetylation-ubiquitination switch of PKM2 regulated the development of glycolysis. Here, we found that Sirt2 deficiency led to impaired glucose tolerance and insulin resistance and induced primary obesity. Sirt2 severely disrupted liver function in mice under metabolic stress, exacerbated the metabolic burden on the liver, and affected glucose metabolism. Sirt2 underwent acetylation modification of lysine 135 of PKM2 through a histidine 187 enzyme active site-dependent effect and reduced ubiquitination of the K48 ubiquitin chain of PKM2. Our findings reveal that the hepatic glucose metabolism links nutrient state to whole-body energetics through the rhythmic regulation of Sirt2.

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Gender Comparisons of Control of Breathing and Metabolism in Conscious Mice Exposed to Cold

Cited by 7 publications

References 43 publications

Enhanced non-eupneic breathing following hypoxic, hypercapnic or hypoxic–hypercapnic gas challenges in conscious mice

Enhanced non-eupneic breathing following hypoxic, hypercapnic or hypoxic–hypercapnic gas challenges in conscious mice

The role of NAD-dependent deacetylase sirtuin-2 in liver metabolic stress through regulating pyruvate kinase M2 ubiquitination

The role of NAD-dependent deacetylase sirtuin-2 in liver metabolic stress through regulating Pyruvate kinase M2 ubiquitination

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