Effects of chronic hypoxia on diaphragm function in deer mice native to high altitude

Dawson, Neal J.; Lyons, Sulayman A.; Henry, D A; Scott, Graham R.

doi:10.1111/apha.13030

Cited by 44 publications

(44 citation statements)

References 58 publications

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“…It is interesting to note that our respiration values are lower than those reported by Braz-Mota et al 2018, although this is expected and has been shown in studies comparing different mitochondrial preparations in other taxa (Saks et al, 1998;Picard et al, 2011;Mahalingam et al, 2017). Mitochondrial respiration rates have classically been normalized using markers of mitochondrial volume, including CS and COX activity (Barrientos, 2002;Larsen et al, 2012;Dawson et al, 2018), and our mitochondrial respiration rates showed an excellent linear relationship (P=0.011, R 2 =0.689; Fig. 2B) with CS activity, suggesting that our measurements were the result of mitochondrion-based oxygen consumption.…”

Section: Resultssupporting

confidence: 45%

“…The maximal activity (V max ) of citrate synthase (CS) and cytochrome c oxidase (COX) is commonly used as a measure of mitochondrial density (Larsen et al, 2012), so would be expected to correlate with measurements of mitochondrial respiration rate per unit mass of tissue. Activity was assayed at 12°C as previously described (Du et al, 2017;Dawson et al, 2018) using a SpectraMaxPlus 384 spectrophotometer (Molecular Devices, Sunnyvale, CA, USA). Samples were homogenized in 20 volumes of ice-cold homogenization buffer [in mmol l −1 : 100 KH 2 PO 4 , 1 EGTA, 1 EDTA and 1 phenylmethylsulfonyl fluoride (PMSF); pH 7.3].…”

Section: Gill Tissue Mitochondrial Enzyme Activitymentioning

confidence: 99%

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Measurement of mitochondrial respiration in permeabilized fish gills

Dawson

Millet

Selman

et al. 2020

Journal of Experimental Biology

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Physiological investigations of fish gills have traditionally centred on the two principal functions of the gills: gas exchange and ion regulation. Mitochondrion-rich cells (MRCs) are primarily found within the gill filaments of fish, and are thought to proliferate in order to increase the ionoregulatory capacity of the gill in response to environmentally induced osmotic challenges. However, surprisingly little attention has been paid to the metabolic function of mitochondria within fish gills. Here, we describe and validate a simple protocol for the permeabilization of fish gills and subsequent measurement of mitochondrial respiration rates in vitro. Our protocol requires only small tissue samples (8 mg), exploits the natural structure of fish gills, does not require mechanical separation of the gill tissue (so is relatively quick to perform), and yields accurate and highly reproducible measurements of respiration rates. It offers great potential for the study of mitochondrial function in gills over a wide range of fish sizes and species.

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Section: Resultssupporting

confidence: 45%

Section: Gill Tissue Mitochondrial Enzyme Activitymentioning

confidence: 99%

Measurement of mitochondrial respiration in permeabilized fish gills

Dawson

Millet

Selman

et al. 2020

Journal of Experimental Biology

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“…This indicates that the bar-headed geese have evolved and adapted their muscle phenotype to sustain prolonged exercise in extreme hypoxia. Some recent studies have examined the changes in skeletal muscle phenotype that have occurred in high-altitude native deer mice (Lui et al, 2015 ; Scott et al, 2015 ; Mahalingam et al, 2017 ; Dawson et al, 2018 ). This rodent model is relevant to study this evolutionary adaptation because deer mice live within a range of altitude from below sea level to ~4,300 m above sea level.…”

Section: Adaptation Of Skeletal Muscle Fiber Type During Exposure Tomentioning

confidence: 99%

Skeletal Muscle Fiber Type in Hypoxia: Adaptation to High-Altitude Exposure and Under Conditions of Pathological Hypoxia

Chaillou

2018

Front. Physiol.

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Skeletal muscle is able to modify its size, and its metabolic/contractile properties in response to a variety of stimuli, such as mechanical stress, neuronal activity, metabolic and hormonal influences, and environmental factors. A reduced oxygen availability, called hypoxia, has been proposed to induce metabolic adaptations and loss of mass in skeletal muscle. In addition, several evidences indicate that muscle fiber-type composition could be affected by hypoxia. The main purpose of this review is to explore the adaptation of skeletal muscle fiber-type composition to exposure to high altitude (ambient hypoxia) and under conditions of pathological hypoxia, including chronic obstructive pulmonary disease (COPD), chronic heart failure (CHF) and obstructive sleep apnea syndrome (OSAS). The muscle fiber-type composition of both adult animals and humans is not markedly altered during chronic exposure to high altitude. However, the fast-to-slow fiber-type transition observed in hind limb muscles during post-natal development is impaired in growing rats exposed to severe altitude. A slow-to-fast transition in fiber type is commonly found in lower limb muscles from patients with COPD and CHF, whereas a transition toward a slower fiber-type profile is often found in the diaphragm muscle in these two pathologies. A slow-to-fast transformation in fiber type is generally observed in the upper airway muscles in rodent models of OSAS. The factors potentially responsible for the adaptation of fiber type under these hypoxic conditions are also discussed in this review. The impaired locomotor activity most likely explains the changes in fiber type composition in growing rats exposed to severe altitude. Furthermore, chronic inactivity and muscle deconditioning could result in the slow-to-fast fiber-type conversion in lower limb muscles during COPD and CHF, while the factors responsible for the adaptation of muscle fiber type during OSAS remain hypothetical. Finally, the role played by cellular hypoxia, hypoxia-inducible factor-1 alpha (HIF-1α), and other molecular regulators in the adaptation of muscle fiber-type composition is described in response to high altitude exposure and conditions of pathological hypoxia.

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“…As it generally improves performance, it will probably also find broad acceptance as lifestyle drug for stressful episodes in life or as preconditioning drug for high altitude adaptation . How the effects of PHDis differ from real hypobaric hypoxia occurring at high altitude and how both conditions interact, are emerging but yet unexplored research fields . Via illegal markets, Roxadustat might also be taken in early pregnancy.…”

Section: Is There a Risk Of Roxadustat Abuse?mentioning

confidence: 99%

“…20,21 How the effects of PHDis differ from real hypobaric hypoxia occurring at high altitude and how both conditions interact, are emerging but yet unexplored research fields. 22,23 Via illegal markets, Roxadustat might also be taken in early pregnancy. If and how PHDis are affecting the development of the embryo or foetus is completely unknown.…”

Section: Roxadustat Abuse?mentioning

confidence: 99%