Emerging roles of PLCγ1 in endothelial biology

Phospholipase C γ1 (PLCγ1) is a member of the PLC family that functions as signal transducer by hydrolyzing membrane lipid to generate second messengers. The unique protein structure of PLCγ1 confers a critical role as a direct effector of VEGFR2 and signaling mediated by other receptor tyrosine kinases. The distinct vascular phenotypes in PLCγ1-deficient animal models and the gain-of-function mutations of PLCγ1 found in human endothelial cancers point to a major physiological role of PLCγ1 in the endothelial system. In this review, we discuss aspects of physiological and molecular function centering around PLCγ1 in the context of endothelial cells and provide a perspective for future investigation.

Melatonin attenuates mitochondrial and metabolic dysfunction caused by leptin deficiency

Leptin, as a nutritional inhibitor by repressing food intake, is critical compromised in the major common forms of obesity. Skeletal muscle is the main effector tissue for energy expenditure modifications by the effect of endocrine axes, such as leptin signaling. Our study has been carried out using skeletal muscle from leptin-deficient animal model, in order to ascertain the importance of this hormone in eating disorders. Here we report that leptin-deficiency stimulates an uncontrolled oxidative phosphorylation metabolism, resulting in an excess of energy production that culminates in mitochondrial dysfunction. Thus, different nutrient sensing pathways are perturbed, loosing proteostasis and promoting lipid anabolism, that induces myofiber degeneration and drives oxidative type I fiber conversion. Melatonin treatment plays a significant role in regulating energy homeostasis and fuel utilization. This study reveals melatonin to be a decisive mitochondrial function-fate regulator, with implications for resembling physiological energy requirements and targeting glycolytic type II fibers recovery.

Acute Muscle Trauma due to Overexercise in an Otherwise Healthy Patient with Cystic Fibrosis

Cystic fibrosis (CF) is one of the most common inherited diseases and is caused by mutations in the CFTR gene. Although the pulmonary and gastrointestinal manifestations of the disease remain in the focus of treatment, recent studies have shown expression of the CFTR gene product in skeletal muscle cells and observed altered intramuscular Ca2+release dynamics in CFTR-deficient animal models. Physical exercise is beneficial for maintaining fitness and well-being in CF patients and constitutes one aspect of modern multimodal treatment, which has considerably increased life span and reduced morbidity. We report on a case of acute muscle trauma resulting from excessive dumbbell exercise in a young adult with cystic fibrosis and describe clinical, laboratory and imaging characteristics of acute exercise-induced muscle injury.