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Montgomery, D. W.

Publications and source records attributed to Montgomery, D. W..

3 recordsLinked to original sources

Rapid blood acid-base regulation by European sea bass (Dicentrarchus labrax) in response to sudden exposure to high environmental CO2

Fish in coastal ecosystems can be exposed to acute variations in CO2 that can approach 1 kPa CO2 (10,000 atm). Coping with this environmental challenge will depend on the ability to rapidly compensate the internal acid-base disturbance caused by sudden exposure to high environmental CO2 (blood and tissue acidosis); however, studies about the speed of acid-base regulatory responses in marine fish are scarce. We observed that upon exposure to ~1 kPa CO2, European sea bass (Dicentrarchus labrax) completely regulate erythrocyte intracellular pH within ~40 minutes, thus restoring haemoglobin-O2 affinity to pre-exposure levels. Moreover, blood pH returned to normal levels within ~2 hours, which is one of the fastest acid-base recoveries documented in any fish. This was achieved via a large upregulation of net acid excretion and accumulation of HCO3- in blood, which increased from ~4 to ~22 mM. While the abundance and intracellular localisation of gill Na+/K+-ATPase (NKA) and Na+/H+ exchanger 3 (NHE3) remained unchanged, the apical surface area of acid-excreting gill ionocytes doubled. This constitutes a novel mechanism for rapidly increasing acid excretion during sudden blood acidosis. Rapid acid-base regulation was completely prevented when the same high CO2 exposure occurred in seawater with experimentally reduced HCO3- and pH, likely because reduced environmental pH inhibited gill H+ excretion via NHE3. The rapid and robust acid-base regulatory responses identified will enable European sea bass to maintain physiological performance during large and sudden CO2 fluctuations that naturally occur in coastal environments. Summary statementEuropean sea bass exposed to 1 kPa (10,000 atm) CO2 regulate blood and red cell pH within 2 hours and 40 minutes, respectively, protecting O2 transport capacity, via enhanced gill acid excretion.

physiology

Temperature and O2, but not CO2, interact to affect aerobic performance of European sea bass (Dicentrarchus labrax)

Climate change causes warming, decreased O2, and increased CO2 in marine systems and responses of organisms will depend on interactive effects between these factors. We provide the first experimental assessment of the interactive effects of warming (14 to 22{degrees}C), reduced O2 ([~]3 - 21 kPa O2), and increased CO2 ([~]400 or [~]1000 {micro}atm ambient CO2) on four indicators of aerobic performance (standard metabolic rate, SMR, maximum metabolic rate, MMR, aerobic scope, and hypoxia tolerance, O2crit), blood chemistry, and O2 transport (P50) of a marine fish, the European sea bass (Dicentrarchus labrax). Warming increased SMR and O2crit (i.e. reduced hypoxia tolerance) as well as MMR in normoxia but there was an interactive effect with O2 so that hypoxia caused larger reductions in MMR and aerobic scope at higher temperatures. Increasing CO2 had minimal effects on SMR, MMR and O2crit and did not show interactive effects with temperature or O2 for any measured variables. Aerobic performance was not linked to changes in blood chemistry or P50. Despite lack of effects of CO2 on aerobic performance, increased CO2 induced 30% mortality of fish exercised in low O2 at 22{degrees}C indicating important threshold effects independent of aerobic performance. Overall, our results show temperature and O2, but not CO2, interact to affect aerobic performance of sea bass, disagreeing with predictions of the oxygen- and capacity-limited thermal tolerance hypothesis.

ecology

Glycosaminoglycan binding motif at S1/S2 proteolytic cleavage site on spike glycoprotein may facilitate novel coronavirus (SARS-CoV-2) host cell entry

Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) has resulted in a pandemic and continues to spread around the globe at an unprecedented rate. To date, no effective therapeutic is available to fight its associated disease, COVID-19. Our discovery of a novel insertion of glycosaminoglycan (GAG)-binding motif at S1/S2 proteolytic cleavage site (681-686 (PRRARS)) and two other GAG-binding-like motifs within SARS-CoV-2 spike glycoprotein (SGP) led us to hypothesize that host cell surface GAGs might be involved in host cell entry of SARS-CoV-2. Using a surface plasmon resonance direct binding assay, we found that both monomeric and trimeric SARS-CoV-2 spike more tightly bind to immobilized heparin (KD = 40 pM and 73 pM, respectively) than the SARS-CoV and MERS-CoV SGPs (500 nM and 1 nM, respectively). In competitive binding studies, the IC50 of heparin, tri-sulfated non-anticoagulant heparan sulfate, and non-anticoagulant low molecular weight heparin against SARS-CoV-2 SGP binding to immobilized heparin were 0.056 M, 0.12 M, and 26.4 M, respectively. Finally, unbiased computational ligand docking indicates that heparan sulfate interacts with the GAG-binding motif at the S1/S2 site on each monomer interface in the trimeric SARS-CoV-2 SGP, and at another site (453-459 (YRLFRKS)) when the receptor-binding domain is in an open conformation. Our study augments our knowledge in SARS-CoV-2 pathogenesis and advances carbohydrate-based COVID-19 therapeutic development.

biochemistry