The mitochondrial lactate oxidation complex: endpoint for carbohydrate carbon disposal.

The lactate shuttle concept has revolutionized our understanding and study of metabolism in physiology, biochemistry, intermediary metabolism, nutrition, and medicine. Seminal findings of the mitochondrial lactate oxidation complex (mLOC) elucidated the architectural structure of its components. Here, we report that the mitochondrial pyruvate carrier (mPC) is an additional member of the mLOC in mouse muscle and C2C12 myoblasts and myotubes.

Species-specific responses to di (2-ethylhexyl) phthalate reveal activation of defense signaling pathways in California sea lion but not in human skeletal muscle cells in primary culture.

Higher antioxidant defenses in marine than terrestrial mammals allow them to cope with oxidative stress associated with diving-induced ischemia/reperfusion. Does this adaptation translate to inherent resistance to other stressors? We analyzed oxidative stress indicators in cells derived from human and California sea lion (Zalophus californianus) skeletal muscle upon exposure to di (2-ethylhexyl) phthalate (DEHP). Human abdominal muscle biopsies were collected from healthy women undergoing planned cesarean surgery.

Extensive longevity and DNA virus-driven adaptation in nearctic bats.

The genus is one of the largest clades of bats, and exhibits some of the most extreme variation in lifespans among mammals alongside unique adaptations to viral tolerance and immune defense. To study the evolution of longevity-associated traits and infectious disease, we generated near-complete genome assemblies and cell lines for 8 closely related species of . Using genome-wide screens of positive selection, analyses of structural variation, and functional experiments in primary cell lines, we identify new patterns of adaptation contributing to longevity, cancer resistance, and viral interactions in bats.

Hypoxia exposure blunts angiogenic signaling and upregulates the antioxidant system in endothelial cells derived from elephant seals.

Background: Elephant seals exhibit extreme hypoxemic tolerance derived from repetitive hypoxia/reoxygenation episodes they experience during diving bouts. Real-time assessment of the molecular changes underlying protection against hypoxic injury in seals remains restricted by their at-sea inaccessibility. Hence, we developed a proliferative arterial endothelial cell culture model from elephant seals and used RNA-seq, functional assays, and confocal microscopy to assess the molecular response to prolonged hypoxia.

Peroxiredoxin 6 suppresses ferroptosis in lung endothelial cells.

Peroxiredoxin 6 (Prdx6) repairs peroxidized membranes by reducing oxidized phospholipids, and by replacing oxidized sn-2 fatty acyl groups through hydrolysis/reacylation by its phospholipase A (aiPLA) and lysophosphatidylcholine acyltransferase activities. Prdx6 is highly expressed in the lung, and intact lungs and cells null for Prdx6 or with single-point mutations that inactivate either Prdx6-peroxidase or aiPLA activity alone exhibit decreased viability, increased lipid peroxidation, and incomplete repair when exposed to paraquat, hyperoxia, or organic peroxides. Ferroptosis is form of cell death driven by the accumulation of phospholipid hydroperoxides.

Hypoxia blunts angiogenic signaling and upregulates the antioxidant system in elephant seal endothelial cells.

Elephant seals experience extreme hypoxemia during diving bouts. Similar depletions in oxygen availability characterize pathologies including myocardial infarction and ischemic stroke in humans, but seals manage these repeated episodes without injury. However, the real-time assessment of the molecular changes underlying protection against hypoxic injury in seals remains restricted by their at-sea inaccessibility.

DEHP exposure impairs human skeletal muscle cell proliferation in primary culture conditions: preliminary study.

The plasticizer di (2-ethylhexyl) phthalate (DEHP) inhibits differentiation, impairs glucose metabolism, and decreases mitochondrial function in murine muscle satellite cells; however, if these effects are translated to human cells is unknown. The goal of this study was to evaluate changes in morphology and proliferation of primary human skeletal muscle cells exposed to DEHP. muscle samples were obtained from healthy women undergoing programed cesarean surgery.

Dolphin leukocytes exhibit an attenuated cytokine response and increase heme oxygenase activity upon exposure to lipopolysaccharides.

Cetaceans exhibit physiological adaptations that allowed the transition to aquatic life, including a robust antioxidant defense system that prevents injury from repeated exposure to ischemia/reperfusion events associated with breath-hold diving. The signaling cascades that characterize ischemic inflammation in humans are well characterized. In contrast, cetaceans' molecular and biochemical mechanisms that confer tolerance to inflammatory events are poorly understood.

Selection on dispersal drives evolution of metabolic capacities for energy production in female wing-polymorphic sand field crickets, Gryllus firmus.

Life history and metabolism covary, but the mechanisms and individual traits responsible for these linkages remain unresolved. Dispersal capability is a critical component of life history that is constrained by metabolic capacities for energy production. Conflicting relationships between metabolism and life histories may be explained by accounting for variation in dispersal and maximal metabolic rates.

"Oxidative stress induced by phthalates in mammals: State of the art and potential biomarkers".

Background: Phthalates, plasticizers that are widely used in consumer products including toys, cosmetics, and food containers, have negative effects in liver, kidney, brain, lung and reproductive system of humans and other mammals.

Objectives: To summarize, describe and discuss the available information on the effects of phthalate exposure in mammals, with emphasis on oxidative stress, and to suggest potential biomarkers of the health risks associated with phthalate exposure.

Methods: An assessment of scientific journals was performed using the PRISMA model for systematic reviews.

Ontogeny of Carbon Monoxide-Related Gene Expression in a Deep-Diving Marine Mammal.

Marine mammals such as northern elephant seals (NES) routinely experience hypoxemia and ischemia-reperfusion events to many tissues during deep dives with no apparent adverse effects. Adaptations to diving include increased antioxidants and elevated oxygen storage capacity associated with high hemoprotein content in blood and muscle. The natural turnover of heme by heme oxygenase enzymes (encoded by and ) produces endogenous carbon monoxide (CO), which is present at high levels in NES blood and has been shown to have cytoprotective effects in laboratory systems exposed to hypoxia.

Chronic AT blockade improves hyperglycemia by decreasing adipocyte inflammation and decreasing hepatic PCK1 and G6PC1 expression in obese rats.

Inappropriate activation of the renin-angiotensin system decreases glucose uptake in peripheral tissues. Chronic angiotensin receptor type 1 (AT) blockade (ARB) increases glucose uptake in skeletal muscle and decreases the abundance of large adipocytes and macrophage infiltration in adipose. However, the contributions of each tissue to the improvement in hyperglycemia in response to AT blockade are not known.

Short-term elevations in glucocorticoids do not alter telomere lengths: A systematic review and meta-analysis of non-primate vertebrate studies.

Background: The neuroendocrine stress response allows vertebrates to cope with stressors via the activation of the Hypothalamic-Pituitary-Adrenal (HPA) axis, which ultimately results in the secretion of glucocorticoids (GCs). Glucocorticoids have pleiotropic effects on behavior and physiology, and might influence telomere length dynamics. During a stress event, GCs mobilize energy towards survival mechanisms rather than to telomere maintenance.

Repeated stimulation of the HPA axis alters white blood cell count without increasing oxidative stress or inflammatory cytokines in fasting elephant seal pups.

The hypothalamic-pituitary-adrenal (HPA) axis controls the release of glucocorticoids, which regulate immune and inflammatory function by modulating cytokines, white blood cells and oxidative stress via glucocorticoid receptor (GR) signaling. Although the response to HPA activation is well characterized in many species, little is known about the impacts of HPA activation during extreme physiological conditions. Hence, we challenged 18 simultaneously fasting and developing elephant seal pups with daily intramuscular injections of adrenocorticotropin (ACTH), a GR antagonist (RU486), or a combination of the two (ACTH+RU486) for 4 days.

Characterization of the Heme Oxygenase 1 From Bottlenose Dolphin (): Evidence of Changes in the Active Site and Purifying Selection.

Cetacea is a clade well-adapted to the aquatic lifestyle, with diverse adaptations and physiological responses, as well as a robust antioxidant defense system. Serious injuries caused by boats and fishing nets are common in bottlenose dolphins (); however, these animals do not show signs of serious infections. Evidence suggests an adaptive response to tissue damage and associated infections in cetaceans.

Potentiation of Acetylcholine-Induced Relaxation of Aorta in Male UC Davis Type 2 Diabetes Mellitus (UCD-T2DM) Rats: Sex-Specific Responses.

Previous reports suggest that diabetes may differentially affect the vascular beds of females and males. The objectives of this study were to examine whether there were (1) sex differences in aortic function and (2) alterations in the relative contribution of endothelium-derived relaxing factors in modulating aortic reactivity in UC Davis Type 2 Diabetes Mellitus (UCD-T2DM) rats. Endothelium-dependent vasorelaxation (EDV) in response to acetylcholine (ACh) was measured in aortic rings before and after exposure to pharmacological inhibitors.

Elephant seal muscle cells adapt to sustained glucocorticoid exposure by shifting their metabolic phenotype.

Elephant seals experience natural periods of prolonged food deprivation while breeding, molting, and undergoing postnatal development. Prolonged food deprivation in elephant seals increases circulating glucocorticoids without inducing muscle atrophy, but the cellular mechanisms that allow elephant seals to cope with such conditions remain elusive. We generated a cellular model and conducted transcriptomic, metabolic, and morphological analyses to study how seal cells adapt to sustained glucocorticoid exposure.

Fasting ameliorates oxidative stress: A review of physiological strategies across life history events in wild vertebrates.

Fasting is a component of many species' life history due to environmental factors or behavioral patterns that limit access to food. Despite metabolic and physiological challenges associated with these life history stages, fasting-adapted wild vertebrates exhibit few if any signs of oxidative stress, suggesting that fasting promotes redox homeostasis. Here we review mammalian, avian, reptilian, amphibian, and piscine examples of animals undergoing fasting during prolonged metabolic suppression (e.

Functional Studies with Primary Cells Provide a System for Genome-to-Phenome Investigations in Marine Mammals.

Marine mammals exhibit some of the most dramatic physiological adaptations in their clade and offer unparalleled insights into the mechanisms driving convergent evolution on relatively short time scales. Some of these adaptations, such as extreme tolerance to hypoxia and prolonged food deprivation, are uncommon among most terrestrial mammals and challenge established metabolic principles of supply and demand balance. Non-targeted omics studies are starting to uncover the genetic foundations of such adaptations, but tools for testing functional significance in these animals are currently lacking.

Antioxidant response to cadmium exposure in primary skeletal muscle cells isolated from humans and elephant seals.

Cadmium (Cd) occurs naturally; however, its concentration can increase with anthropogenic activities. Excess Cd increases reactive oxygen species (ROS) production and oxidative damage, which can lead to pathological conditions. Marine mammals accumulate Cd in the liver and the kidney; yet, there are no reports of Cd-associated tissue damage in whales, seals or dolphins.

Natural Tolerance to Ischemia and Hypoxemia in Diving Mammals: A Review.

Reperfusion injury follows ischemia/reperfusion events occurring during myocardial infarction, stroke, embolism, and other peripheral vascular diseases. Decreased blood flow and reduced oxygen tension during ischemic episodes activate cellular pathways that upregulate pro-inflammatory signaling and promote oxidant generation. Reperfusion after ischemia recruits inflammatory cells to the vascular wall, further exacerbating oxidant production and ultimately resulting in cell death, tissue injury, and organ dysfunction.