Hypoxia Tolerance of Two Killifish Species.

Hypoxia tolerance in aquatic ectotherms involves a suite of behavioral and physiological responses at the organismal, tissue, and cellular levels. The current study evaluated two closely related killifish species (Fundulus heteroclitus, Fundulus majalis) to evaluate responses to acute moderate and acute severe hypoxia. Routine metabolic rate and loss of equilibrium were assessed, followed by analysis in skeletal muscle of markers of oxidative damage to proteins (2,4-DNPH), lipids (4-HNE), and DNA (8-OHdG), hypoxia signaling (HIF1α, HIF2α), cellular energy state (p-AMPK: AMPK), and protein degradation (Ubiquitin, LC3B, Calpain 2, Hsp70).

Lectin binding to pectoral fin of neonate little skates reared under ambient and projected-end-of-century temperature regimes.

The glycosylation of macromolecules can vary both among tissue structural components and by adverse conditions, potentially providing an alternative marker of stress in organisms. Lectins are proteins that bind carbohydrate moieties and lectin histochemistry is a common method to visualize microstructures in biological specimens and diagnose pathophysiological states in human tissues known to alter glycan profiles. However, this technique is not commonly used to assess broad-spectrum changes in cellular glycosylation in response to environmental stressors.

Relationship between red blood cell lifespan and endogenous carbon monoxide in the common bottlenose dolphin and beluga.

Certain deep-diving marine mammals [i.e., northern elephant seal (), Weddell seal ()] have blood carbon monoxide (CO) levels that are comparable with those of chronic cigarette smokers.

Intraspecific variation in muscle growth of two distinct populations of Port Jackson sharks under projected end-of-century temperatures.

Although pervasive, the effects of climate change vary regionally, possibly resulting in differential behavioral, physiological, and/or phenotypic responses among populations within broadly distributed species. Juvenile Port Jackson sharks (Heterodontus portusjacksoni) from eastern and southern Australia were reared at their current (17.6 °C Adelaide, South Australia [SA]; 20.

Microvascular anatomy suggests varying aerobic activity levels in the adipose tissues of diving tetrapods.

Adipose tissue has many important functions including metabolic energy storage, endocrine functions, thermoregulation and structural support. Given these varied functions, the microvascular characteristics within the tissue will have important roles in determining rates/limits of exchange of nutrients, waste, gases and molecular signaling molecules between adipose tissue and blood. Studies on skeletal muscle have suggested that tissues with higher aerobic capacity contain higher microvascular density (MVD) with lower diffusion distances (DD) than less aerobically active tissues.

A higher mitochondrial content is associated with greater oxidative damage, oxidative defenses, protein synthesis and ATP turnover in resting skeletal muscle.

An unavoidable consequence of aerobic metabolism is the production of reactive oxygen species (ROS). Mitochondria have historically been considered the primary source of ROS; however, recent literature has highlighted the uncertainty in primary ROS production sites and it is unclear how variation in mitochondrial density influences ROS-induced damage and protein turnover. Fish skeletal muscle is composed of distinct, highly aerobic red muscle and anaerobic white muscle, offering an excellent model system in which to evaluate the relationship of tissue aerobic capacity and ROS-induced damage under baseline conditions.

Endosomal-lysosomal dysfunction in metabolic diseases and Alzheimer's disease.

The endosomal-lysosomal pathways and related autophagic processes are responsible for proteostasis, involving complexes between lysosomes and autophagosomes. Lysosomes are a key component of homeostasis, involved in cell signaling, metabolism, and quality control, and they experience functional compromise in metabolic diseases, aging, and neurodegenerative diseases. Many genetic mutations and risk factor genes associated with proteinopathies, as well as with metabolic diseases like diabetes, negatively influence endocytic trafficking and autophagic clearance.

Low-dose caffeine administration increases fatty acid utilization and mitochondrial turnover in C2C12 skeletal myotubes.

Caffeine has been shown to directly increase fatty acid oxidation, in part, by promoting mitochondrial biogenesis. Mitochondrial biogenesis is often coupled with mitophagy, the autophagy-lysosomal degradation of mitochondria. Increased mitochondrial biogenesis and mitophagy promote mitochondrial turnover, which can enhance aerobic metabolism.

Locomotor muscle morphology of three species of pelagic delphinids.

The locomotor muscle morphology of diving mammals yields insights into how they utilize their environment and partition resources. This study examined a primary locomotor muscle, the longissimus, in three closely related, similarly sized pelagic delphinids (n = 7-9 adults of each species) that exhibit different habitat and depth preferences. The Atlantic spotted dolphin (Stenella frontalis) is a relatively shallow diver, inhabiting continental shelf waters; the striped (Stenella coeruleoalba) and short-beaked common (Delphinus delphis) dolphins are sympatric, deep-water species that dive to different depths.

β-guanidinopropionic acid and metformin differentially impact autophagy, mitochondria and cellular morphology in developing C2C12 muscle cells.

The serine/threonine kinase AMP-activated protein kinase (AMPK) is a drug target for the treatment of obesity and type 2 diabetes (T2D). Metformin, a widely prescribed anti-hyperglycemic agent, and β-guanidinopropionic acid (β-GPA), a dietary supplement and creatine analog, have been shown to increase activity of AMPK. Macroautophagy is an intracellular degradation pathway for aggregated proteins and dysfunctional organelles, which can be mediated by AMPK.

The effects of dietary β-guanidinopropionic acid on growth and muscle fiber development in juvenile red porgy, Pagrus pagrus.

β-guanidinopropionic acid (β-GPA) has been used in mammalian models to reduce intracellular phosphocreatine (PCr) concentration, which in turn lowers the energetic state of cells. This leads to changes in signaling pathways that attempt to re-establish energetic homeostasis. Changes in those pathways elicit effects similar to those of exercise such as changes in body and muscle growth, metabolism, endurance and health.

Transparent anemone shrimp () become opaque after exercise and physiological stress in correlation with increased hemolymph perfusion.

Whole-body transparency, an effective camouflage strategy in many aquatic species, can be disrupted by environmental and/or physiological stressors. We found that tail-flip escape responses temporarily disrupt the transparency of the anemone shrimp After as few as three tail flips, the previously transparent abdominal muscle became cloudy. Eliciting additional tail flips to the point of exhaustion (16±1 s.

-GPA treatment leads to elevated basal metabolic rate and enhanced hypoxic exercise tolerance in mice.

Treatments that increase basal metabolic rate (BMR) and enhance exercise capacity may be useful therapeutic approaches for treating conditions such as type 2 diabetes, obesity, and associated circulatory problems. -guanidinopropionic acid (-GPA) supplementation decreases high-energy phosphate concentrations, such as ATP and phosphocreatine (PCr) resulting in an energetic challenge that is similar to both exercise programs and hypoxic conditions. In this study, we administered -GPA to mice for 2 or 6 weeks, and investigated the effect on muscle energetic status, body and muscle mass, muscle capillarity, BMR, and normoxic and hypoxic exercise tolerance (NET and HET, respectively).

Dietary supplementation of β-guanidinopropionic acid (βGPA) reduces whole-body and skeletal muscle growth in young CD-1 mice.

Increased AMP-activated protein kinase (AMPK) activity leads to enhanced fatty acid utilization, while also promoting increased ubiquitin-dependent proteolysis (UDP) in mammalian skeletal muscle. β-guanidinopropionic acid (βGPA) is a commercially available dietary supplement that has been shown to promote an AMPK-dependent increase in fatty acid utilization and aerobic capacity in mammals by compromising creatine kinase function. However, it remains unknown if continuous βGPA supplementation can negatively impact skeletal muscle growth in a rapidly growing juvenile.

Effects of resveratrol on growth and skeletal muscle physiology of juvenile southern flounder.

Resveratrol is a naturally occurring antioxidant that has been widely studied in mammals due to its potential to extend lifespan. However, antioxidants may also limit protein damage and therefore reduce rates of protein degradation, providing a potential avenue for enhancing growth in an aquaculture setting. The present study tested the hypotheses that in Southern flounder, Paralichthys lethostigma, resveratrol would decrease protein carbonylation and 4-HNE (indicators of protein and lipid oxidative damage, respectively), levels of ubiquitinylation and LC3 (indicators of non-lysosomal and lysosomal protein degradation, respectively), while having no effect on S6K activation (indicator of protein synthesis).

Large fibre size in skeletal muscle is metabolically advantageous.

Skeletal muscle fibre size is highly variable, and while diffusion appears to limit maximal fibre size, there is no paradigm for the control of minimal size. The optimal fibre size hypothesis posits that the reduced surface area to volume in larger fibres reduces the metabolic cost of maintaining the membrane potential, and so fibres attain an optimal size that minimizes metabolic cost while avoiding diffusion limitation. Here we examine changes during hypertrophic fibre growth in metabolic cost and activity of the Na⁺-K⁺-ATPase in white skeletal muscle from crustaceans and fishes.

Locomotor muscle profile of a deep (Kogia breviceps) versus shallow (Tursiops truncatus) diving cetacean.

When a marine mammal dives, breathing and locomotion are mechanically uncoupled, and its locomotor muscle must power swimming when oxygen is limited. The morphology of that muscle provides insight into both its oxygen storage capacity and its rate of oxygen consumption. This study investigated the m.

Ring bands in fish skeletal muscle: reorienting the myofibrils and microtubule cytoskeleton within a single cell.

Skeletal muscle cells (fibers) contract by shortening their parallel subunits, the myofibrils. Here we show a novel pattern of myofibril orientation in white muscle fibers of large black sea bass, Centropristis striata. Up to 48% of the white fibers in fish >1168 g had peripheral myofibrils undergoing an ∼90(o) shift in orientation.

Nuclear DNA content variation associated with muscle fiber hypertrophic growth in fishes.

Muscle fiber hypertrophic growth can lead to an increase in the myonuclear domain (MND), leading to greater diffusion distances within the cytoplasmic volume that each nucleus services. We tested the hypothesis that hypertrophic growth in the white muscle of fishes was associated with increases in the mean DNA content of nuclei, which may be a strategy to offset increasing diffusion constraints. DAPI-stained chicken erythrocytes standards and image analysis were used to estimate nuclear DNA content in erythrocytes and muscle fibers from 17 fish species.

An evaluation of muscle maintenance costs during fiber hypertrophy in the lobster Homarus americanus: are larger muscle fibers cheaper to maintain?

Large muscle fiber size imposes constraints on muscle function while imparting no obvious advantages, making it difficult to explain why muscle fibers are among the largest cell type. Johnston and colleagues proposed the 'optimal fiber size' hypothesis, which states that some fish have large fibers that balance the need for short diffusion distances against metabolic cost savings associated with large fibers. We tested this hypothesis in hypertrophically growing fibers in the lobster Homarus americanus.

Growth patterns and nuclear distribution in white muscle fibers from black sea bass, Centropristis striata: evidence for the influence of diffusion.

This study investigated the influence of fiber size on the distribution of nuclei and fiber growth patterns in white muscle of black sea bass, Centropristis striata, ranging in body mass from 0.45 to 4840 g. Nuclei were counted in 1 μm optical sections using confocal microscopy of DAPIand Acridine-Orange-stained muscle fibers.

Molecules in motion: influences of diffusion on metabolic structure and function in skeletal muscle.

Metabolic processes are often represented as a group of metabolites that interact through enzymatic reactions, thus forming a network of linked biochemical pathways. Implicit in this view is that diffusion of metabolites to and from enzymes is very fast compared with reaction rates, and metabolic fluxes are therefore almost exclusively dictated by catalytic properties. However, diffusion may exert greater control over the rates of reactions through: (1) an increase in reaction rates; (2) an increase in diffusion distances; or (3) a decrease in the relevant diffusion coefficients.

Scaling with body mass of mitochondrial respiration from the white muscle of three phylogenetically, morphologically and behaviorally disparate teleost fishes.

White muscle (WM) fibers in many fishes often increase in size from <50 μm in juveniles to >250 μm in adults. This leads to increases in intracellular diffusion distances that may impact the scaling with body mass of muscle metabolism. We have previously found similar negative scaling of aerobic capacity (mitochondrial volume density, V(mt)) and the rate of an aerobic process (post-contractile phosphocreatine recovery) in fish WM.

Nuclear DNA content variation associated with muscle fiber hypertrophic growth in decapod crustaceans.

We tested the hypothesis that hypertrophic muscle growth in decapod crustaceans is associated with increases in both the number of nuclei per fiber and nuclear DNA content. The DNA-localizing fluorochrome DAPI (4',6-diamidino-2-phenylindole) and chicken erythrocyte standards were used with static microspectrophotometry and image analysis to estimate nuclear DNA content in hemocytes and muscle fibers from eight decapod crustacean species: Farfantepenaeus aztecus, Palaemonetes pugio, Panulirus argus, Homarus americanus, Procambarus clarkii, Cambarus bartonii, Callinectes sapidus, and Menippe mercenaria. Mean diploid (2C) values in hemocytes ranged from 3.

A skeletal muscle model of extreme hypertrophic growth reveals the influence of diffusion on cellular design.

Muscle fibers that power swimming in the blue crab Callinectes sapidus are <80 microm in diameter in juveniles but grow hypertrophically, exceeding 600 microm in adults. Therefore, intracellular diffusion distances become progressively greater as the animals grow and, in adults, vastly exceed those in most cells. This developmental trajectory makes C.