Muscle Plasticity and β2-Adrenergic Receptors: Adaptive Responses of β2-Adrenergic Receptor Expression to Muscle Hypertrophy and Atrophy

We discuss the functional roles of β2-adrenergic receptors in skeletal muscle hypertrophy and atrophy as well as the adaptive responses of β2-adrenergic receptor expression to anabolic and catabolic conditions. β2-Adrenergic receptor stimulation using anabolic drugs increases muscle mass by promoting muscle protein synthesis and/or attenuating protein degradation. These effects are prevented by the downregulation of the receptor. Endurance training improves oxidative performance partly by increasing β2-adrenergic receptor density in exercise-recruited slow-twitch muscles. However, excessive stimulation of β2-adrenergic receptors negates their beneficial effects. Although the preventive effects of β2-adrenergic receptor stimulation on atrophy induced by muscle disuse and catabolic hormones or drugs are observed, these catabolic conditions decrease β2-adrenergic receptor expression in slow-twitch muscles. These findings present evidence against the use of β2-adrenergic agonists in therapy for muscle wasting and weakness. Thus, β2-adrenergic receptors in the skeletal muscles play an important physiological role in the regulation of protein and energy balance

Involvement of both protein kinase C and G proteins in superoxide production after IgE triggering in guinea pig eosinophils

ABSTRACTTo study the function and mechanism of eosinophils via the low affinity IgE receptor (FceRII), we examined the production of 02 metabolites by measuring the luminol-dependent chemiluminescence (LDCL) response and the generation of cysteinyl leukotrienes. Eosinophils obtained from guinea pig peritoneal fluid sensitized with horse serum were purified. Luminol-dependent chemiluminescence was induced by stimulation with monoclonal anti-CD23 antibody, but not by mouse serum (controls). The mean (±SEM) value of LDCL was 20.6±1.3X103 c.p.m. This reaction consisted of an initial rapid phase and a propagation phase and ended within lOmin. Guinea pig eosinophils were histochemically stained with monoclonal anti-CD23 antibody. The major product generated in the LDCL response was superoxide, as determined by the measurement of superoxide by cytochrome c reduction and the complete inhibitory effect of superoxide dismutase on the LDCL response. Pretreatment with either pertussis toxin or cholera toxin inhibited the LDCL reaction. Depletion of bivalent ions by EDTA inhibited this response and the protein kinase C inhibitor D-sphingosin inhibited both 1-oleoyl-2-acetyl-glycerol-induced and FcϵRII-mediated LDCL. These findings suggest that the NADPH-protein kinase C pathway may be involved in the FceRII-mediated LDCL response in guinea pig eosinophils

Physiological Role of Alveolar Macrophage in Acute Lower Respiratory Tract Infection: Phagocytosis and Aging

Acute lower respiratory tract infections (LRTIs) are the deadliest communicable diseases. Inhaled pathogens that reach the alveoli are eliminated by lung-resident alveolar macrophages. Bacteria and fungi are detected and phagocytosed by specific pattern recognition receptors (PRRs) that are highly expressed in alveolar macrophages. In addition, early pro-inflammatory responses assist alveolar macrophages in the efficient phagocytosis of these pathogens. Viruses are also directly or indirectly endocytosed by pinocytosis or opsonization, respectively, whereas alveolar macrophages contribute to the prevention of pneumonia by removing endogenous dead cells through an alternate type of phagocytosis, efferocytosis. Macrophage phagocytosis and efferocytosis require not only sufficient expression of the relevant PRRs but also the coordinated interplay of intracellular factors that regulate engulfment. Given the current situation in which emerging infectious diseases spread worldwide, this chapter summarizes the physiological roles of alveolar macrophages in acute LRTIs, focusing on phagocytosis, pro-inflammatory responses, efferocytosis, and their regulatory machinery. This chapter also reviews recent insights into age-associated dysfunction of alveolar macrophages and discusses their relevance to vulnerability to acute LRTIs in the elderly population

The Molecular Mechanism Underlying Continuous Exercise Training-Induced Adaptive Changes of Lipolysis in White Adipose Cells

Physical exercise accelerates the mobilization of free fatty acids from white adipocytes to provide fuel for energy. This happens in several tissues and helps to regulate a whole-body state of metabolism. Under these conditions, the hydrolysis of triacylglycerol (TG) that is found in white adipocytes is known to be augmented via the activation of these lipolytic events, which is referred to as the “lipolytic cascade.” Indeed, evidence has shown that the lipolytic responses in white adipocytes are upregulated by continuous exercise training (ET) through the adaptive changes in molecules that constitute the lipolytic cascade. During the past few decades, many lipolysis-related molecules have been identified. Of note, the discovery of a new lipase, known as adipose triglyceride lipase, has redefined the existing concepts of the hormone-sensitive lipase-dependent hydrolysis of TG in white adipocytes. This review outlines the alterations in the lipolytic molecules of white adipocytes that result from ET, which includes the molecular regulation of TG lipases through the lipolytic cascade

Paroxysmal nocturnal hemoglobinuria in systemic lupus erythematosus: a case report

<p>Abstract</p> <p>Introduction</p> <p>Paroxysmal nocturnal hemoglobinuria is an acquired disorder of hemopoiesis and is characterized by recurrent episodes of intravascular hemolysis due to an increased sensitivity to complement-mediated hemolysis. Systemic lupus erythematosus with paroxysmal nocturnal hemoglobinuria is very rare. We report a case of paroxysmal nocturnal hemoglobinuria that developed in a patient with systemic lupus erythematosus and lupus nephritis.</p> <p>Case presentation</p> <p>A 29-year-old Mongolian woman had systemic lupus erythematosus, which manifested only as skin lesions when she was 12 years old. She had leg edema and proteinuria when she was 23 years old, and a renal biopsy revealed lupus nephritis (World Health Organization type IV). She had been treated with steroids and immunosuppressant therapy. At 29, she had headaches, nausea, general fatigue, and severe pancytopenia and was admitted to our hospital. A laboratory evaluation showed hemolytic anemia. Further examination showed a neutrophil alkaline phosphatase score of 46 points, a CD55 value of 18%, and a CD59 value of 78.6%. The results of Ham test and sugar water tests were positive. The constellation of symptoms throughout the clinical course and the laboratory findings suggested paroxysmal nocturnal hemoglobinuria.</p> <p>Conclusions</p> <p>To the best of our knowledge, systemic lupus erythematosus with paroxysmal nocturnal hemoglobinuria is very rare. Clinicians should be aware of the association between autoimmune and hematological diseases.</p

Exercise Training Attenuates the Dysregulated Expression of Adipokines and Oxidative Stress in White Adipose Tissue

Obesity-induced inflammatory changes in white adipose tissue (WAT), which caused dysregulated expression of inflammation-related adipokines involving tumor necrosis factor-α and monocyte chemoattractant protein-1, contribute to the development of insulin resistance. Moreover, current literature reports state that WAT generates reactive oxygen species (ROS), and the enhanced production of ROS in obese WAT has been closely associated with the dysregulated expression of adipokines in WAT. Therefore, the reduction in excess WAT and oxidative stress that results from obesity is thought to be one of the important strategies in preventing and improving lifestyle-related diseases. Exercise training (TR) not only brings about a decrease in WAT mass but also attenuates obesity-induced dysregulated expression of the adipokines in WAT. Furthermore, some reports indicate that TR affects the generation of oxidative stress in WAT. This review outlines the impact of TR on the expression of inflammation-related adipokines and oxidative stress in WAT

Posttranscriptional Suppression of Lipopolysaccharide-Stimulated Inflammatory Responses by Macrophages in Middle-Aged Mice: A Possible Role for Eukaryotic Initiation Factor 2α

The intensities of macrophage inflammatory responses to bacterial components gradually decrease with age. Given that a reduced rate of protein synthesis is a common age-related biochemical change, which is partially mediated by increased phosphorylation of eukaryotic initiation factor-2α (eIF-2α), we investigated the mechanism responsible for the deterioration of macrophage inflammatory responses, focusing specifically on the age-related biochemical changes in middle-aged mice. Peritoneal macrophages isolated from 2-month-old (young) and 12-month-old (middle-aged) male BALB/c mice were stimulated with lipopolysaccharide (LPS). Although LPS-stimulated secretion of tumor necrosis factor-α (TNF-α) by the macrophages from middle-aged mice was significantly lower than that from young mice, LPS caused marked increases in levels of TNF-α mRNA in macrophages from middle-aged as well as young mice. Moreover, LPS evoked similar levels of phosphorylation of c-Jun N-terminal kinase (JNK) and nuclear factor-κB (NF-κB) in young and middle-aged mice. In contrast, the basal level of phosphorylated eIF-2α in macrophages from middle-aged mice was higher than that in macrophages from young mice. Salubrinal, an inhibitor of the phosphatase activity that dephosphorylates eIF-2α, suppressed the LPS-stimulated inflammatory responses in a murine macrophage cell line RAW264.7. These results suggest that posttranscriptional suppression of macrophage inflammatory responses during middle age requires phosphorylation of eIF-2α