Muscle lipofuscin content and satellite cell volume is increased after high altitude exposure in humans

Summary Muscle ultrastructural changes during a typical expedition to the Himalayas were analyzed by taking muscle biopsies from seven climbers before and after their sojourn at high altitude (over 5000 m for 8 weeks). M. vastus lateralis samples were analyzed morphometrically from electron micrographs. A quantitative evaluation was made of lipofuscin, satellite cells and myonuclei. Significant increases of the volume densities of lipofuscin (+235%) and satellite cells (+215%) were observed.     

Satellite cells in the regenerated and regrafted skeletal muscles of rats

Soleus (SOL) muscles were grafted into extensor digitorum longus (EDL) muscle beds (EDL-first-graft). Sixty days later, some mature EDL-first-grafts were regrafted into their own beds (EDL-second-grafts). Fully regenerated muscle fibers and satellite cells were observed in both types of mature grafts. The ratios of satellite cell nuclei per total nuclei (myonuclei and satellite cell nuclei) were 4.81 +/- 0.47% for EDL-2nd graft, 4.26 +/- 0.51% for EDL-1st-graft, 4.30 +/- 0.33% for control SOL, and 3.30 +/- 0.18% for control EDL. It is thought that satellite cells are required for the repeated activity of muscle fiber regeneration. The persistance of satellite cells in EDL-second-grafts suggests that satellite cells are not depleted during the first grafting, making second-grafts possible.     

Satellite cells in the regenerated and regrafted skeletal muscles of rats

Summary Soleus (SOL) muscles were grafted into extensor digitorum longus (EDL) muscle beds (EDL-first-graft). Sixty days later, some mature EDL-first-grafts were regrafted into their own beds (EDL-second-grafts). Fully regenerated muscle fibers and satellite cells were observed in both types of mature grafts. The ratios of satellite cell nuclei per total nuclei (myonuclei and satellite cell nuclei) were 4.81±0.47% for EDL-2nd graft, 4.26±0.51% for EDL-1st-graft, 4.30±0.33% for control SOL, and 3.30±0.18% for control EDL. It is thought that satellite cells are required for the repeated activity of muscle fiber regeneration. The persistance of satellite cells in EDL-second-grafts suggests that satellite cells are not depleted during the first grafting, making second-grafts possible.     

Culture in low levels of oxygen enhances in vitro proliferation potential of satellite cells from old skeletal muscles

The proliferation ability of satellite cells (considered the 'stem cells' of mature myofibers) declines with increasing age when cultured under standard cell culture conditions of 21% oxygen. However, actual oxygen levels in the intact myofiber in vivo are an order of magnitude lower. No studies to date have addressed the issue of whether culturing satellite cells from old muscles under more 'physiologic' conditions would enhance their proliferation and/or differentiation ability. Therefore, we analyzed satellite cells derived from 31-month-old rats in standard cultures with 21% O₂ and in lowered (∼3%) O₂. Under the lowered O₂ conditions, we noted a remarkable increase in the percentage of large-sized colonies, activation of cell cycle progression factors, phosphorylation of Akt, and downregulation of the cell cycle inhibitor p27^Kip1. These data suggest that lower O₂ levels provide a milieu that stimulates proliferation by allowing continued cell cycle progression, to result ultimately in the enhanced in vitro replicative life span of the old satellite cells. Such a method therefore provides an improved means for the ex vivo generation of progenitor satellite cell populations for potential therapeutic stem cell transplantation. Received 20 April 2001; received after revision 28 May 2001; accepted 31 May 2001     

Cadmium-induced lipofuscins and effect of zinc on hepatopancreas cells inIdotea baltica

Histological investigation revealed cadmium-induced lipofuscin formation in hepatopancreatic cells of the crustacean isopod,Idotea baltica. A comparison of lipofuscin induction by cadmium and by copper showed that cadmium has a weaker peroxidative action than copper. The effect of cadmium was reduced by the simultaneous presence of zinc, which on its own was ineffective in lipofuscin induction. A tentative explantation of the interactive effects of these materials is suggested.     

Synergistic effect of acute hypoxia on flow-induced release of ATP from cultured endothelial cells

Human umbilical vein endothelial cells (HUVECs) in primary cultures were perfused under normoxic or hypoxic conditions. These cells were stimulated twice for 3 min by increased flow (from 0.5 to 3.0 ml/min). Under hypoxic conditions the basal release of ATP was the same as under normoxic conditions, but during increased flow the release was greater (0.58±0.07>0.32±0.04 pmoles/ml/10⁶ cells (+78%), for the first period of stimulation; 0.39±0.05>0.22±0.03 pmoles/ml/10⁶ cells (+79%) for the second period). Further experiments with sequential increments in flow rate showed that under both normoxic and hypoxic conditions, a positive correlation existed between ATP release and the rate of flow but there was always more ATP released under hypoxic conditions regardless of the flow rate.HUVECs in secondary culture (second passage) were similarly stimulated. No differences were observed between normoxic and hypoxic conditions. In both cases, the quantity of ATP released during high flow (0.050±0.004 pmoles/ml/10⁶ cells) was significantly smaller than the quantity of ATP released during low flow (0.09±0.01 pmoles/ml/10⁶ cells).To conclude, since hypoxia alone did not affect ATP release, there appears to be a synergistic relationship between increased shear stress and hypoxia in the stimulation of ATP release from HUVECs. Moreover, the release of ATP under these conditions seems to be a property of highly differentiated endothelial cells.     

Effect of air ionization of blood serotonin in vitro.

The effect of negative and positive air ionisation on siliconized blood serotonin was studied in vitro. The experiments showed that within 10 min positive ionisation increased serotonin levels in total blood (+40%), plasma (+90%), erythrocytes (+50%) and thrombocytes (+240%). On the other hand, negative ionization (10 min) lowered the serotonin content of total blood (-30%), plasma (-42.5%), erythrocytes (-41.7%) and thrombocytes (-72.3%), thus confirming the 'Krueger Effect' in vitro.     

Lipofuscin accumulation in squirrel monkey spinal cord consequent to protein malnutrition during gestation.

The formation of lipofuscin pigment in the anterior horn cells of the cervical spinal cord has shown in the fetuses and neonates under the extrinsic influence of maternal protein deprivation during the gestation period in the squirrel monkeys.     

Lipofuscin accumulation in squirrel monkey spinal cord consequent to protein malnutrition during gestation

Summary The formation of lipofuscin pigment in the anterior horn cells of the cervical spinal cord has shown in the fetuses and neonates under the extrinsic influence of maternal protein deprivation during the gestation period in the squirrel monkeys.Acknowledgments. This work was supported by US PHS grants RR-00165 HD-06087 from National Institute of Health. The technical assistance of Miss Judie Seubert is greatly appreciated.     

Pleiotropic effects of sonic hedgehog on muscle satellite cells

Muscle satellite cells are believed to form a stable, self-renewing pool of stem cells in adult muscle where they function in tissue growth and repair. A regulatory disruption of growth and differentiation of these cells is assumed to result in tumor formation. Here we provide for the first time evidence that sonic hedgehog (Shh) regulates the cell fate of adult muscle satellite cells in mammals. Shh promotes cell division of satellite cells (and of the related model C2C12 cells) and prevents their differentiation into multinucleated myotubes. In addition, Shh inhibits caspase-3 activation and apoptosis induced by serum deprivation. These effects of Shh are reversed by simultaneous administration of cyclopamine, a specific inhibitor of the Shh pathway. Taken together, Shh acts as a proliferation and survival factor of satellite cells in the adult muscle. Our results support the hypothesis of the rhabdomyosarcoma origin from satellite cells and suggest a role for Shh in this process.Received 23 February 2005; received after revision 2 May 2005; accepted 9 June 2005     

The comparative biology of neuromelanin and lipofuscin in the human brain

Neuromelanin and lipofuscin are two pigments produced within the human brain that, until recently, were considered inert cellular waste products of little interest to neuroscience. Recent research has increased our understanding of the nature and interactions of these pigments with their cellular environment and suggests that these pigments may, indeed, influence cellular function. The physical appearance and distribution of the pigments within the human brain differ, but both accumulate in the aging brain and the pigments share some structural features. Lipofuscin accumulation has been implicated in postmitotic cell aging, while neuromelanin is suggested to function as an iron-regulatory molecule with possible protective functions within the cells which produce this pigment. This review presents comparative aspects of the biology of neuromelanin and lipofuscin, as well as a discussion of their hypothesized functions in brain and their possible roles in aging and neurodegenerative disease.     

Reduction of efferent renal nerve activity by propranolol in rabbits]

During intravenous infusion of propranolol (0.3--0.8 mg/kg) in the Rabbit, systolic arterial pressure is decreased (-6.5 +/- 4.2 mmHg) and electrical activity recorded from central end of the renal nerve is reduced significantly (-8.7 +/- 14.-%) with regard to the activity obtained, at the same pressure levels, by hemorrhage (+7.9 +/- 6.4%; p less than 0.25) or by intravenous infusion of the peripheral vasodilator sodium nitroprusside (+14.1 +/- 9.9%; p less than 0.01).     

Effect of air ionization on blood serotonin in vitro

Summary The effect of negative and positive air ionisation on siliconized blood serotonin was studied in vitro. The experiments showed that within 10 min positive ionisation increased serotonin levels in total blood (+40%), plasma (+90%), erythrocytes (+50%) and thrombocytes (+200%). On the other hand, negative ionization (10 min) lowered the serotonin content of total blood (–30%), plasma (–42.5%), erythrocytes (–41.7%) and thrombocytes (–72.3%), thus confirming the Krueger Effect in vitro.This research was generously supported by a grant from the Joint Research Fund of the Hebrew University and Hadassah, and Dr. and Mrs.Leonard Appleby of Palmbeach, Florida.Acknowledgment: Our thanks are due to Mr.B. Shalita, Mrs.Zippora Adar and Mrs.Olga Fradkin for devoted technical assistance.     

Effect of acetylhomocysteine thiolactone on nucleolar cytology and lipofuscinogenesis in electric lobe neurons

Treatment with acetylhomocysteine thiolactone significantly reduces the cellular level of lipofuscin in neurons of the electric lobe of Torpedo marmorata. At the same time, this drug produces a 45% decrease in nucleolar volume in these neurons, reflecting decreased cellular synthetic activity.     

Effect of acetylhomocysteine thiolactone on nucleolar cytology and lipofuscinogenesis in electric lobe neurons

Summary Treatment with acetylhomocysteine thiolactone significantly reduces the cellular level of lipofuscin in neurons of the electric lobe ofTorpedo marmorata. At the same time, this drug produces a 45% decrease in nucleolar volume in these neurons, reflecting decreased cellular synthetic activity.     

Satellite DNA (II) from sea urchin (Lytechinus variegatus) sperm

When DNA isolated from freshly collected sperm of sea urchin (Lytechinus variegatus) is centrifuged to equilibrium in CsCl, 2 heavy satellite bands appear beside the main band DNA. Satellite DNA (II) appears in between the main band DNA (rho = 1.695 g/cm3) and the rDNA satellite (rho = 1.722 g/cm3). Satellite DNA (II) has a buoyant density 1.710 g/cm3, corresponding to 50% GC content. It is speculated that the satellite DNA (II), which appears to be of high mol. wt, might contain the sequences complementary to histone mRNA.     

α-Tocopherol reduces fluorescent age pigment levels in heart and brain of young mice

Summary The levels of fluorometrically measured lipofuscin, or age pigment, were significantly lower in the brain and the heart of -tocopherol (vitamin E)-injected mice as compared to untreated control mice at 3 and at 5 months of age.     

Satellite DNA from the beetleTenebrio molitor

Summary A 142 base-pair satellite DNA from the mealworm beetle,Tenebrio molitor, has been cloned and sequenced. The satellite DNA is revealed by making a restriction digest of genomic DNA with either EcoRI or Hinfl, and constitutes approximately 49% of the genomic DNA. The presence of huge amounts of satellite DNA correlates well with the prominent blocks of heterochromatin found in tenebrionid beetles. A similar restriction digest ofXanthogaleruca luteola genomic DNA does not release a prominent satellite component.     

Early stimulation of protein kinase activity during hormonal meiosis reinitiation in starfish ovocytes]

Total endogenous protein kinase activity has been compared in homogenates prepared from Marthasterias glacialis and Asterias rubens oocytes treated or not by 1-methyladenine, the hormone which triggers meiosis reinitiation. A 5 mn treatment at the threshold 10(-7) M concentration causes a significant increase (+ 20%) of these activities. This stimulation is maintained or even enhanced when homogenates are complemented with exogenous histones.     

Pentobarbital-induced increase of rat liver phosphoprotein phosphatase

Résumé Le pentobarbital provoque un accroissement important de l'activité de la phosphoprotein-phosphatase extramicrosomiale du foie du rat. L'accroissement de l'activité de l'enzyme se produit dejà 20 min après l'administration du médicament (+40%) et dure autant que le traitement (+50–70%). Le niveau de l'induction dépend de la dose du pentobarbital. L'induction est bloquée par l'administration simultanée du cycloheximide ou du SKF 525-A.