Apelin Deficiency Accelerates the Progression of Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the selective loss of motor neurons. Recent studies have implicated that chronic hypoxia and insufficient vascular endothelial growth factor (VEGF)-dependent neuroprotection may lead to the degeneration of motor neurons in ALS. Expression of apelin, an endogenous ligand for the G protein-coupled receptor APJ, is regulated by hypoxia. In addition, recent reports suggest that apelin protects neurons against glutamate-induced excitotoxicity. Here, we examined whether apelin is an endogenous neuroprotective factor using SOD1G93A mouse model of ALS. In mouse CNS tissues, the highest expressions of both apelin and APJ mRNAs were detected in spinal cord. APJ immunoreactivity was observed in neuronal cell bodies located in gray matter of spinal cord. Although apelin mRNA expression in the spinal cord of wild-type mice was not changed from 4 to 18 weeks age, that of SOD1G93A mice was reduced along with the paralytic phenotype. In addition, double mutant apelin-deficient and SOD1G93A displayed the disease phenotypes earlier than SOD1G93A littermates. Immunohistochemical observation revealed that the number of motor neurons was decreased and microglia were activated in the spinal cord of the double mutant mice, indicating that apelin deficiency pathologically accelerated the progression of ALS. Furthermore, we showed that apelin enhanced the protective effect of VEGF on H2O2-induced neuronal death in primary neurons. These results suggest that apelin/APJ system in the spinal cord has a neuroprotective effect against the pathogenesis of ALS

INVESTIGATION OF ELECTROMAGNETIC FIELDS ON CARDIAC CELLS

International audienceExposure to electromagnetic fields (EMF) has become a sensitive topic for the public health. Despite accumulative exposure of humans to EMF, their effects on oxidative stress and cell death status in cardiac cells have not been studied. In the present study, the properties of transverse electromagnetic (TEM) cells were explored by varying the frequency and the power at first, then the temporal shape of the source EMF in a second time. In addition, we evaluated the effects of EMF on antioxidant and cell death/survival status of H9C2 cardiomyoblasts. Using reverse transcription quantitative PCR (RT-qPCR), we analyzed mRNA expression of antioxidant enzyme catalase, anti-apoptotic factor Bcl-2 and pro-apoptotic factor Bax in H9C2 cells subjected to 915 MHz for 24h, 48h and 72h. The exposure of H9C2 cells to EMF for 24h, 48h and 72h did not significantly change mRNA expression levels of catalase, Bcl-2 and Bax. Therefore, these results indicate that short-term exposure to EMF did not influence antioxidant and cell death status incardiomyoblasts

IL-26 in the induced sputum is associated with the level of systemic inflammation, lung functions and body weight in COPD patients

Lesia Savchenko,1 Marina Mykytiuk,1 Mathieu Cinato,2,3 Helene Tronchere,2,3 Oxana Kunduzova,2,3 Igor Kaidashev1 1Ukrainian Medical Stomatological Academy, Poltava, Ukraine; 2National Institute of Health and Medical Research (INSERM) U1048, Toulouse, France; 3Department of Internal Medicine, University of Toulouse, UPS, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France Background: Chronic inflammatory process is the main link in COPD pathogenesis, which causes structural changes in the respiratory tract and lungs. In overweight patients, an adipose tissue could contribute to activation of the inflammatory process. Therefore, it is highly important to identify potential biomarkers of inflammation for patients with COPD and obesity. The aim of this study was to investigate the role of interleukin-26 (IL-26) and evaluate the relationship between the level of systemic inflammation, lung function, and body mass index (BMI) in patients with COPD.Patients and methods: Eighty-three patients with COPD in the stable condition (stage 2 according to the 2016 Global Initiative for Chronic Obstructive Lung Disease recommendations), aged 40–70 years, were included in the study. All patients were divided into 2 groups: obese (n=53) (BMI – 30.0–39.9 kg/m2) and non-obese (n=30) (BMI – 18.5–24.9 kg/m2). We conducted patients’ examination, spirometry, induced the sputum, determined the level of C-reactive protein (CRP), leptin in serum and IL-26 in sputum.Results: Obese and non-obese COPD patients had a significant increase in IL-26 compared with healthy subjects by 2.3 and 2.6 (P=0.0003). We also observed a higher level of CRP by 1.38 times (P=0.0008), compared with the rate in non-obese COPD patients, and by 1.8 times (P=0.015) higher concentration level of leptin compared with healthy subjects. The sputum IL-26 level had positive correlation with BMI, CRP, and leptin, and a negative – with forced expiratory volume in 1 second (FEV1) and FEV1/forced vital capacity. Leptin level had positive correlation with BMI and CRP, and negative with FEV1, FEV1/forced vital capacity.Conclusion: Obese COPD patients had a higher level of persistent systemic inflammation than non-obese ones, which is confirmed by a significant increase of CRP and leptin in serum. The data confirm that IL-26 can be considered as a perspective marker to detect the inflammation level in lung tissue of COPD patients. Keywords: COPD, obesity, interleukin-26, induced sputu

Apelin/APJ signaling system: a potential link between adipose tissue and endothelial angiogenic processes.

International audienceAdipose tissue is an active endocrine organ that produces a variety of secretory factors involved in the initiation of angiogenic processes. The bioactive peptide apelin is the endogenous ligand of the G protein-coupled receptor, APJ. Here we investigated the potential role of apelin and its receptor, APJ, in the angiogenic responses of human endothelial cells and the development of a functional vascular network in a model of adipose tissue development in mice. Treatment of human umbilical vein endothelial cells with apelin dose-dependently increased angiogenic responses, including endothelial cell migration, proliferation, and Matrigel(R) capillary tubelike structure formation. These endothelial effects of apelin were due to activation of APJ, because siRNA directed against APJ, which led to long-lasting down-regulation of APJ mRNA, abolished cell migration induced by apelin in contrast to control nonsilencing siRNA. Hypoxia up-regulated the expression of apelin in 3T3F442A adipocytes, and we therefore determined whether apelin could play a role in adipose tissue angiogenesis in vivo. Epididymal white adipose tissue (EWAT) transplantation was performed as a model of adipose tissue angiogenesis. Transplantation led to increased apelin mRNA levels 2 and 5 days after transplantation associated with tissue hypoxia, as evidenced by hydroxyprobe staining on tissue sections. Graft revascularization evolved in parallel, as the first functional vessels in EWAT grafts were observed 2 days after transplantation and a strong angiogenic response was apparent on day 14. This was confirmed by determination of graft hemoglobin levels, which are indicative of functional vascularization and were strongly increased 5 and 14 days after transplantation. The role of apelin in the graft neovascularization was then assessed by local delivery of stable complex apelin-targeting siRNA leading to dramatically reduced apelin mRNA levels and vascularization (quantified by hemogloblin content) in grafted EWAT on day 5 when compared with control siRNA. Taken together, our data provide the first evidence that apelin/APJ signaling pathways play a critical role in the development of the functional vascular network in adipose tissue. In addition, we have shown that adipocyte-derived apelin can be up-regulated by hypoxia. These findings provide novel insights into the complex relationship between adipose tissue and endothelial vascular function and may lead to new therapeutic strategies to modulate angiogenesis

Towards a Large-Scale Assessment of the Relationship Between Biological and Chronological Aging: The Inspire Mouse Cohort

International audienceAging is the major risk factor for the development of chronic diseases. After decades of research focused on extending lifespan, current efforts seek primarily to promote healthy aging. Recent advances suggest that biological processes linked to aging are more reliable than chronological age to account for an individual's functional status, i.e. frail or robust. It is becoming increasingly apparent that biological aging may be detectable as a progressive loss of resilience much earlier than the appearance of clinical signs of frailty. In this context, the INSPIRE program was built to identify the mechanisms of accelerated aging and the early biological signs predicting frailty and pathological aging. To address this issue, we designed a cohort of outbred SWISS mice (1576 male and female mice) in which we will continuously monitor spontaneous and voluntary physical activity from 6 to 24 months of age under either normal or high fat/high sucrose diet. At different age points (6, 12, 18, 24 months), multiorgan functional phenotyping will be carried out to identify early signs of organ dysfunction and generate a large biological fluids/feces/organs biobank (100,000 samples). A comprehensive correlation between functional and biological phenotypes will be assessed to determine: 1) the early signs of biological aging and their relationship with chronological age; 2) the role of dietary and exercise interventions on accelerating or decelerating the rate of biological aging; and 3) novel targets for the promotion of healthy aging. All the functional and omics data, as well as the biobank generated in the framework of the INSPIRE cohort will be available to the aging scientific community. The present article describes the scientific background and the strategies employed for the design of the INSPIRE Mouse cohort