Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endothelial dysfunction, referring to a disturbance in the vascular homeostasis, has been implicated in many disease conditions including ischemic/reperfusion injury and atherosclerosis. Endothelial mitochondria have been increasingly recognized as a regulator of calcium homeostasis which has implications in the execution of diverse cellular events and energy production. The mitochondrial calcium uniporter complex through which calcium enters the mitochondria is composed of several proteins, including the pore-forming subunit MCU and its regulators MCUR1, MICU1, and MICU2. Mitochondrial calcium overload leads to opening of MPTP (mitochondrial permeability transition pore) and results in apoptotic cell death. Whereas, blockage of calcium entry into the mitochondria results in reduced ATP production thereby activates AMPK-mediated pro-survival autophagy. Here, we investigated the expression of mitochondrial calcium uniporter complex components (MCU, MCUR1, MICU1, and MICU2), induction of autophagy and apoptotic cell death in endothelial cells in response to oxygen-glucose deprivation. Human pulmonary microvascular endothelial cells (HPMVECs) were subjected to oxygen-glucose deprivation (OGD) at 3-h timepoints up to 12 h. Interestingly, except MCUR1 which was significantly downregulated, all other components of the uniporter (MCU, MICU1, and MICU2) remained unchanged. MCUR1 downregulation has been shown to activate AMPK mediated pro-survival autophagy. Similarly, MCUR1 downregulation in response to OGD resulted in AMPK phosphorylation and LC3 processing indicating the activation of pro-survival autophagy. Despite the activation of autophagy, OGD induced Caspase-mediated apoptotic cell death. Blockade of autophagy did not reduce OGD-induced apoptotic cell death whereas serum starvation conferred enough cellular and functional protection. In conclusion, the autophagic flux induced by MCUR1 downregulation in response to OGD is insufficient in protecting endothelial cells from undergoing apoptotic cell death and requires enhancement of autophagic flux by additional means such as serum starvation.
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PMID:Oxygen Glucose Deprivation Induced Prosurvival Autophagy Is Insufficient to Rescue Endothelial Function. 3304 54

The history of hunger is a story about natural disasters and wars, but, on the other hand, also about the investigation of evolutionary defense mechanisms concerning quantitative food shortages. The article presents how fasting and the experimental starving oriented the development of physiology, and it is based on a comparative analysis of monographs and articles on starvation in the medical context from library collections and the PubMed database. Over the centuries, doctors have believed that fasting has a beneficial effect on health, and they recommended a restrictive diet during an illness. In the 19th century, the growth of modern physiology was determined by experimental fasting of human subjects and animals. Furthermore, undernourishment and chronic hunger in large populations were recognized as a threat to public health for the first time. During both world wars, depriving civilians of food became a strategy of combat and a method of genocide. The mass nature of war hunger motivated doctors to research the pathophysiology of starvation and refeeding of emaciated people, even in the ghetto or concentration camps. After the Second World War, the invention of the scanning electron microscope enabled systematic studies on the effects of starvation on the human body. As a result, the pathogenesis of atherosclerosis and the cellular metabolism of cholesterol at the submolecular level were clarified. At the turn of the 21st century, the research on the metabolic response to starvation shed new light on atherogenesis and the link between lipid and carbohydrate metabolism.
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PMID:The changing face of hunger: from fasting to the concept of atherogenesis. 3320 95


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