Phorbol ester and diacylglycerol induce protein phosphorylation at tyrosine

The phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA) is an efficient tumour promoter in vivo. In vitro, TPA activates the phospholipid- and Ca2+-dependent protein kinase, kinase C. This activation is believed to reflect the structural similarity between TPA and diacylglycerol, the endogenous protein kinase C activator which is produced in vivo by hydrolysis of phosphatidylinositol (reviewed in ref. 3). Protein kinase C phosphorylates protein substrates at serine and threonine residues in vitro. The effects of TPA on cultured fibroblasts--including enhanced hexose uptake, disruption of actin stress fibres and growth stimulation--are very similar to those induced by certain retrovirus transforming proteins and by peptide growth factors such as epidermal growth factor (EGF), platelet-derived growth factor (PDGF) and multiplication-stimulating activity (MSA). These transforming proteins and mitogenic agents seem to act by inducing tyrosine-specific protein phosphorylation. Such observations suggested that some of the effects of TPA in vivo may be mediated by protein phosphorylation at tyrosine residues. A 42,000-molecular weight (42 K) polypeptide was previously shown to be phosphorylated at tyrosine in cells transformed by avian sarcoma viruses and in cells stimulated by EGF, PDGF or MSA (J. Cooper, personal communication and refs 11 and 12; this polypeptide was originally designated 43 K or spot n in ref. 10). We show here that this polypeptide also becomes phosphorylated at tyrosine in cells treated with TPA. Furthermore, exogenously added diacylglycerol likewise stimulates the phosphorylation of this protein at tyrosine.     

Experimental study in rats to reduce carbon monoxide in the blood induced by cigarette smoke, by inhaling oxygen at atmospheric pressure]

When animals are exposed to cigarette smoke, the concentration of carbon monoxide in blood is rapidly increased, so that intensive inhalation tests cannot be carried out. A simple apparatus is described to expose Rats alternatively to cigarette smoke and to oxygen in order to reduce the concentration of carbon monoxide in the blood. This method makes it possible to increase the daily administration of smoke considerably; nevertheless, under such conditions, lung tumors were not observed.     

Systemic oxygen transport and erythropoiesis in the mouse

Summary Removal of 15% of blood volume in the mouse increases erythropoiesis by a factor of 2.2 when measured 12 h after bleeding. Exposure of normal mice to 40% reduced barometric pressure for the same period of time increases erythropoiesis only by a factor of 1.6. The response to hypoxia takes place in the presence of a 40% reduction of oxygen consumption and tissue-venous P_{o 2}, changes which are concomitant with a 5-fold increase in plasma erythropoietin activity. The larger response in anemic animals on the other hand occurs without any detectable change in these parameters. These results cast serious doubts about the interpretation of the quantitative homeostatic control of erythropoiesis based solely on the action of erythropoietin.Acknowledgments. This work was supported by a grant from the Consejo Nacional de Investigaciones Científicas y Técnicas de la República Argentina. We thank Isabel Zingariello for excellent technical assistance.     

Glucose-6-phosphatase activity in experimental tuberculosis and following isoniazid treatment

Zusammenfassung Bei den tuberkulösen Meerschweinchen wurde in der Niere eine erhöhte Aktivität der Glukose-6-Phosphatase beobachtet. Isoniazid hat die erhöhte Aktivität des Enzyms nicht erniedrigt, wenn es tuberkulösen Tieren vom 8. bis zum 38. Tage nach der Infektion oral verabreicht wurde. Es wird angenommen, dass die erhöhte Aktivität Ausdruck der Adaptionsfähigkeit von Glukose-6-Phosphatase ist.

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Galesburg State Research Hospital, Galesburg, Illinois, USA.