Three weeks of erythropoietin treatment hampers skeletal muscle mitochondrial biogenesis in rats

The blood O₂-carrying capacity is maintained by the O₂-regulated production of erythropoietin (Epo), which stimulates the proliferation and survival of red blood cell progenitors. Epo has been thought to act exclusively on erythroid progenitor cells. However, recent studies have identified the erythropoietin receptor (EpoR) in other cells, such as neurons, astrocytes, microglia, heart, cancer cell lines, and skeletal muscle provides evidence for a potential role of Epo in other tissues. In this study we aimed to determine the effect of recombinant human erythropoietin (rHuEpo) on skeletal muscle adaptations such as mitochondrial biogenesis, myogenesis, and angiogenesis in different muscle fibre types. Fourteen male Wistar rats were randomly divided into two experimental groups, and saline or rHuEpo (300?IU) was administered subcutaneously three times a week for 3?weeks. We evaluated the protein expression of intermediates involved in the mitochondrial biogenesis cascade, the myogenic cascade, and in angiogenesis in the oxidative soleus muscle and in the glycolytic gastrocnemius muscle. Contrary to our expectations, rHuEpo significantly hampered the mitochondrial biogenesis pathway in gastrocnemius muscle (PGC-1??, mTFA and cytochrome c). We did not find any effect of the treatment on cellular signals of myogenesis (MyoD and Myf5) or angiogenesis (VEGF) in either soleus or gastrocnemius muscles. Finally, we found no significant effect on the maximal aerobic velocity at the end of the experiment in the rHuEpo-treated animals. Our findings suggest that 3?weeks of rHuEpo treatment, which generates an increase of oxygen carrying capacity, can affect mitochondrial biogenesis in a muscle fibre-specific dependent manner.     

Effect of chlorgyline on gamma-aminobutyric acid levels in hyperoxia

Chlorgyline, an inhibitor of type A monoamine oxidase, administered to rats prevented oxygen-induced decrease in gamma-aminobutyric acid brain content in hyperoxia. At the same time chlorgyline had an overall protective effect, increasing two-fold the period prior to the development of oxygen convulsions. The data suggest an important role of the modification of monoamine oxidase catalytic properties in the development of oxygen-induced intoxication and, particularly, in the decrease of gamma-aminobutyric acid content in hyperoxia.     

Effect of hyperoxia on the oxyhemoglobin dissociation curve in various periods of aging

Gas composition of the arterial and venous blood and the oxyhemoglobin dissociation curve were determined before and after 20 minutes of oxygen inhalation in 9 apparently healthy subjects aged 60 to 74 years and in 9 young subjects aged 19 to 32 years. In hyperoxia of younger subjects, there was a shift to the left of both the oxyhemoglobin dissociation curve of the native blood and standard dissociation curve (pH 7.4). In old age, the shift to the left of the standard dissociation curve due to hypoxia was quite negligible and statistically insignificant, whereas in the native blood it was entirely absent because of the increased blood PCO2 and associated Bohr effect.     

Aquaporin 1 is important for maintaining secretory granule biogenesis in endocrine cells

Aquaporins (AQPs), a family of water channels expressed in epithelial cells, function to transport water in a bidirectional manner to facilitate transepithelial fluid absorption and secretion. Additionally, AQP1 and AQP5 are found in pancreatic zymogen granules and synaptic vesicles and are involved in vesicle swelling and exocytosis in exocrine cells and neurons. Here, we show AQP1 is in dense-core secretory granule (DCSG) membranes of endocrine tissue: pituitary and adrenal medulla. The need for AQP1 in endocrine cell function was examined by stable transfection of AQP1 antisense RNA into AtT20 cells, a pituitary cell line, to down-regulate AQP1 expression. These AQP1-deficient cells showed more than 60% depletion of DCSGs and significantly decreased DCSG protein levels, including proopiomelanocotin/pro-ATCH and prohormone convertase 1/3, but not non-DCSG proteins. Pulse-chase studies revealed that whereas DCSG protein synthesis was unaffected, approximately 50% of the newly synthesized proopiomelanocortin was degraded within 1 h. Low levels of ACTH were released upon stimulation, indicating that the small number of DCSGs that were made in the presence of the residual AQP1 were functionally competent for exocytosis. Analysis of anterior pituitaries from AQP1 knockout mice showed reduced prohormone convertase 1/3, carboxypeptidase E, and ACTH levels compared to wild-type mice demonstrating that our results observed in AtT20 cells can be extended to the animal model. Thus, AQP1 is important for maintaining DCSG biogenesis and normal levels of hormone secretion in pituitary endocrine cells.     

Effect of hyperoxia on liver necrosis induced by hepatotoxins

We have tested the effects of hyperbaric oxygen on necrosis of rat liver induced by the administration of several toxins. The extent of liver necrosis was determined 24 h after the administration of the toxins by measurement of serum levels of alanine and aspartate amino-transferases and by histologic and ultrastructural analyses. Treatment with hyperbaric oxygen decreases carbon tetrachloride (CCl4)-induced necrosis in a manner dependent upon duration and pressure of oxygen exposure. Pretreatment of rats with phenobarbital diminishes this protective effect. Hyperbaric oxygen treatment before or immediately after CCl4 intoxication is protective. Loss of protection is rapid; hyperbaric oxygen treatment 6 h after CCl4 intoxication augments the liver necrosis. No delayed necrogenic effects of CCl4 are seen in the animals treated with hyperbaric oxygen immediately. Hyperbaric oxygen augments the liver necrosis induced by acetaminophen, bromobenzene, dimethylnitrosamine or thioacetamide. This augmented necrosis is averted by prolonged treatment with hyperbaric oxygen. Hyperbaric oxygen has no effect on liver injury induced by galactosamine or lipopolysaccharide. We conclude that hyperoxia decreases the hepatic necrosis induced by compounds which undergo reductive biotransformation by the cytochrome P-450 monooxygenase system; hyperoxia augments the necrosis induced by compounds which undergo oxidative biotransformation by this system. Biotransformation of toxins appears to be nonspecifically inhibited by hyperoxic exposure of long duration.     

Effect of beta-endorphin on endocrine function

It has been disclosed that beta-endorphin exerts marked effect on the secretion of ACTH, prolactin, corticosterone, aldosterone and somatotrophin formation in the pituitary but does not produce any effect on blood thyrotropin. Maximal rise in the concentration of the hormones was seen at the 20th minute, despite the fact that an elevation in the content of some hormones was recorded at the 5th minute following intravenous injection of beta-endorphin. At the 60th minute after beta-endorphin injection the content of prolactin, corticosterone and aldosterone in the blood dropped to the control level, while ACTH content remained significantly higher than in intact animals. One of the possible mechanisms underlying the action of beta-endorphin on the secretion of the hormones indicated might be the changes in the ratio of brain monoamines (a decrease in dopamine).