Browsing by Author "Yu, Tianzheng"

Filter results by typing the first few letters
Now showing 1 - 6 of 6
  • Thumbnail Image
    ItemOpen Access
    5-Hydroxymethylfurfural reduces skeletal muscle superoxide production and modifies force production in rats exposed to hypobaric hypoxia.
    (Physiological reports, 2023-07) Ciarlone, Geoffrey E; Swift, Joshua M; Williams, Brian T; Mahon, Richard T; Roney, Nicholas G; Yu, Tianzheng; Gasier, Heath G
    Decreased blood-tissue oxygenation at high altitude (HA) increases mitochondrial oxidant production and reduces exercise capacity. 5-Hydroxymethylfurfural (5-HMF) is an antioxidant that increases hemoglobin's binding affinity for oxygen. For these reasons, we hypothesized that 5-HMF would improve muscle performance in rats exposed to a simulated HA of ~5500 m. A secondary objective was to measure mitochondrial activity and dynamic regulation of fission and fusion because they are linked processes impacted by HA. Fisher 344 rats received 5-HMF (40 mg/kg/day) or vehicle during exposure to sea level or HA for 72 h. Right ankle plantarflexor muscle function was measured pre- and post-exposure. Post-exposure measurements included arterial blood gas and complete blood count, flexor digitorum brevis myofiber superoxide production and mitochondrial membrane potential (ΔΨm), and mitochondrial dynamic regulation in the soleus muscle. HA reduced blood oxygenation, increased superoxide levels and lowered ΔΨm, responses that were accompanied by decreased peak isometric torque and force production at frequencies >75 Hz. 5-HMF increased isometric force production and lowered oxidant production at sea level. In HA exposed animals, 5-HMF prevented a decline in isometric force production at 75-125 Hz, prevented an increase in superoxide levels, further decreased ΔΨm, and increased mitochondrial fusion 2 protein expression. These results suggest that 5-HMF may prevent a decrease in hypoxic force production during submaximal isometric contractions by an antioxidant mechanism.
  • Thumbnail Image
    ItemOpen Access
    Acclimation of C2C12 myoblasts to physiological glucose concentrations for in vitro diabetes research
    (Life Sciences, 2018-10) Dohl, Jacob; Foldi, Jonathan; Heller, Julian; Gasier, Heath G; Deuster, Patricia A; Yu, Tianzheng
  • Thumbnail Image
    ItemOpen Access
    Astaxanthin but not quercetin preserves mitochondrial integrity and function, ameliorates oxidative stress, and reduces heat‐induced skeletal muscle injury
    (Journal of Cellular Physiology, 2019-08) Yu, Tianzheng; Dohl, Jacob; Chen, Yifan; Gasier, Heath G; Deuster, Patricia A
  • Thumbnail Image
    ItemOpen Access
    Carbon Monoxide and Exercise Prevents Diet-Induced Obesity and Metabolic Dysregulation Without Affecting Bone.
    (Obesity (Silver Spring, Md.), 2020-05) Gasier, Heath G; Yu, Tianzheng; Swift, Joshua M; Metzger, Corrine E; McNerny, Erin M; Swallow, Elizabeth A; Piantadosi, Claude A; Allen, Matthew R

    Objective

    Carbon monoxide (CO) may counteract obesity and metabolic dysfunction in rodents consuming high-fat diets, but the skeletal effects are not understood. This study investigated whether low-dose inhaled CO (250 ppm) with or without moderate intensity aerobic exercise (3 h/wk) would limit diet-induced obesity and metabolic dysregulation and preserve bone health.

    Methods

    Obesity-resistant (OR) rats served as controls, and obesity-prone (OP) rats were randomized to sedentary, sedentary plus CO, exercise, or CO plus exercise. For 10 weeks, OP rats consumed a high-fat, high-sucrose diet, whereas OR rats consumed a low-fat control diet. Measurements included indicators of obesity and metabolism, bone turnover markers, femoral geometry and microarchitecture, bone mechanical properties, and tibial morphometry.

    Results

    A high-fat, high-sucrose diet led to obesity, hyperinsulinemia, and hyperleptinemia, without impacting bone. CO alone led only to a modest reduction in weight gain. Exercise attenuated weight gain and improved the metabolic profile; however, bone fragility increased. Combined CO and exercise led to body mass reduction and a metabolic state similar to control OR rats and prevented the exercise-induced increase in bone fragility.

    Conclusions

    CO and aerobic exercise training prevent obesity and metabolic sequelae of nutrient excess while stabilizing bone physiology.
  • Thumbnail Image
    ItemOpen Access
    Curcumin Ameliorates Heat-Induced Injury through NADPH Oxidase-Dependent Redox Signaling and Mitochondrial Preservation in C2C12 Myoblasts and Mouse Skeletal Muscle.
    (The Journal of nutrition, 2020-09) Yu, Tianzheng; Dohl, Jacob; Wang, Li; Chen, Yifan; Gasier, Heath G; Deuster, Patricia A

    Background

    Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and the mitochondrial electron transport chain are the primary sources of reactive oxygen species (ROS). Previous studies have shown that severe heat exposure damages mitochondria and causes excessive mitochondrial ROS production that contributes to the pathogenesis of heat-related illnesses.

    Objectives

    We tested whether the antioxidant curcumin could protect against heat-induced mitochondrial dysfunction and skeletal muscle injury, and characterized the possible mechanism.

    Methods

    Mouse C2C12 myoblasts and rat flexor digitorum brevis (FDB) myofibers were treated with 5 μM curcumin; adult male C57BL/6J mice received daily curcumin (15, 50, or 100 mg/kg body weight) by gavage for 10 consecutive days. We compared ROS levels and mitochondrial morphology and function between treatment and nontreatment groups under unheated or heat conditions, and investigated the upstream mechanism and the downstream effect of curcumin-regulated ROS production.

    Results

    In C2C12 myoblasts, curcumin prevented heat-induced mitochondrial fragmentation, ROS overproduction, and apoptosis (all P < 0.05). Curcumin treatment for 2 and 4 h at 37°C induced increases in ROS levels by 42% and 59% (dihydroethidium-derived fluorescence), accompanied by increases in NADPH oxidase protein expression by 24% and 32%, respectively (all P < 0.01). In curcumin-treated cells, chemical inhibition and genetic knockdown of NADPH oxidase restored ROS to levels similar to those of controls, indicating NADPH oxidase mediates curcumin-stimulated ROS production. Moreover, curcumin induced ROS-dependent shifting of the mitochondrial fission-fusion balance toward fusion, and increases in mitochondrial mass by 143% and membrane potential by 30% (both P < 0.01). In rat FDB myofibers and mouse gastrocnemius muscles, curcumin preserved mitochondrial morphology and function during heat stress, and prevented heat-induced mitochondrial ROS overproduction and tissue injury (all P < 0.05).

    Conclusions

    Curcumin regulates ROS hormesis favoring mitochondrial fusion/elongation, biogenesis, and improved function in rodent skeletal muscle. Curcumin may be an effective therapeutic target for heat-related illness and other mitochondrial diseases.
  • Thumbnail Image
    ItemOpen Access
    Skeletal muscle mitochondrial fragmentation and impaired bioenergetics from nutrient overload are prevented by carbon monoxide.
    (American journal of physiology. Cell physiology, 2020-10) Gasier, Heath G; Dohl, Jacob; Suliman, Hagir B; Piantadosi, Claude A; Yu, Tianzheng
    Nutrient excess increases skeletal muscle oxidant production and mitochondrial fragmentation that may result in impaired mitochondrial function, a hallmark of skeletal muscle insulin resistance. This led us to explore whether an endogenous gas molecule, carbon monoxide (CO), which is thought to prevent weight gain and metabolic dysfunction in mice consuming high-fat diets, alters mitochondrial morphology and respiration in C2C12 myoblasts exposed to high glucose (15.6 mM) and high fat (250 µM BSA-palmitate) (HGHF). Also, skeletal muscle mitochondrial morphology, distribution, respiration, and energy expenditure were examined in obese resistant (OR) and obese prone (OP) rats that consumed a high-fat and high-sucrose diet for 10 wk with or without intermittent low-dose inhaled CO and/or exercise training. In cells exposed to HGHF, superoxide production, mitochondrial membrane potential (ΔΨm), mitochondrial fission regulatory protein dynamin-related protein 1 (Drp1) and mitochondrial fragmentation increased, while mitochondrial respiratory capacity was reduced. CO decreased HGHF-induced superoxide production, Drp1 protein levels and mitochondrial fragmentation, maintained ΔΨm, and increased mitochondrial respiratory capacity. In comparison with lean OR rats, OP rats had smaller skeletal muscle mitochondria that contained disorganized cristae, a normal mitochondrial distribution, but reduced citrate synthase protein expression, normal respiratory responses, and a lower energy expenditure. The combination of inhaled CO and exercise produced the greatest effect on mitochondrial morphology, increasing ADP-stimulated respiration in the presence of pyruvate, and preventing a decline in resting energy expenditure. These data support a therapeutic role for CO and exercise in preserving mitochondrial morphology and respiration during metabolic overload.