Red blood cells protect endothelial cells against H2O2-mediated but not hyperoxia-induced damage

We studied the effect of intact red blood cells on the exogenous H2O2-mediated damage as well as on the hyperoxia-induced injury of cultured endothelial cells. Red blood cells protected endothelial cells against H2O2-mediated injury efficiently, but had no effect on the hyperoxia-induced damage. Failure of red blood cells to protect endothelial cells against hyperoxia-induced injury was not due to hemolysis. Furthermore, hyperoxia-exposed red blood cells were still capable of protecting endothelial cells against H2O2-mediated damage.     

Structure and function of tyrosine kinase receptors

Over the past ten years, several growth factor receptors have been shown to be ligand-regulated tyrosine kinases. Tyrosine kinase activity is essential for signal transmission, suggesting that phosphorylation cascades may play an important role. Considerable effort has gone into understanding the structure and function of tyrosine kinase receptors in order to define their mechanisms of signal transmission. However, the protein substrates of the receptor kinases have proven to be difficult to isolate and clone. This review focuses on the receptors for insulin, epidermal growth factor, and platelet-derived growth factor. They are all tyrosine kinases, but emerging evidence suggests that they utilize multiple separate signal transduction pathways. Work carried out during the next several years should yield considerable insight into the complexity of the components which interact with these tyrosine kinase receptors to regulate cellular growth and metabolism.     

Expression of two cytochromes P450 involved in carcinogen activation in a human colon cell line

Cytochrome P450 is known to cause carcinogen activation and correspondingly increased cancer risk in animal models. In order to determine whether P450 in the colon may be involved in cancer development in the human, the human colon cell line LS174T was examined for the presence of various cytochromes P450. Two isozymes of P450 were identified in the human cell line. Expression of P450IAl or IA2 was increased by treatment of the cell line with benzanthracene; the induction was demonstrated by an increase in RNA hybridizing to a probe for P4501Al and by ethoxyresorufin deethylation activity. Western analysis of microsomes isolated from human colon tissue also demonstrated the presence of P4501A1, as well as a form which cross-reacted to an antibody to human P450IIC9. Another isozyme, P450IIE1, was identified by polymerase chain reaction amplification of RNA from LS174T cells. These results underscore the presence of cytochromes P450 in colonic tissue and provide a basis for the involvement of isozyme-specific P450 mediated reactions in carcinogenesis of the colon.Some of the data presented here were taken from a thesis submitted by D.K.H. in partial fulfillment of the requirements for the Ph.D. degree in the University of Texas Graduate School of Biomedical Sciences.     

Evidence for a role of calmodulin in the regulation of prolactin gene expression

Epidermal growth factor (EGF) stimulates prolactin (PRL) gene expression in GH3 cells in a Ca2+-dependent manner (White, B. A., and Bancroft, F. C. (1983) J. Biol. Chem. 258, 4618-4622). The present report shows that the phenothiazine, calmidazolium (compound R 24571), blocks the ability of EGF plus Ca2+ to increase levels of PRL mRNA. Calmidazolium inhibition of this response is dose dependent in the range of 0.05-1.00 microM. Total inhibition of the response was consistently obtained at a level of calmidazolium (0.5 microM) that had no effect on total cytoplasmic RNA synthesis, total cytoplasmic protein synthesis, cell viability, or extent of EGF plus Ca2+-induced cell aggregation. The drug inhibited the increase in PRL mRNA when given immediately before or 48 h after treatment with EGF plus Ca2+. Another calmodulin inhibitor, W13, similarly blocked the ability of EGF plus Ca2+ to stimulate PRL mRNA, whereas the less active analog, W12, had little effect. These results implicate Ca2+-binding proteins such as calmodulin in the mechanism of action of EGF in GH3 cells, and, therefore, provide further evidence for a role of intracellular Ca2+ in the regulation of the expression of a specific eukaryotic gene, the PRL gene.     

Seasonal changes in serum glucose and condition of the plaice, Pleuronectes platessa L.

Monthly sampling of plaice caught off the north-east coast of Scotland between February 1983 and May 1984 revealed a seasonal increase in condition factor, hepatosomatic index and serum glucose, which appeared to be related to the period of active feeding. The spleen indices followed a similar seasonal increase, although this was not statistically significant, while the kidney indices showed little change over the 16 months. The peak for the gonadosomatic index was in February/March 1984, but among these plaice (aged 4–5 years) there were still large numbers of immature males and females and there was no increase in 1983. Apart from the hepatosomatic index for January 1984, there was no significant difference between male and female plaice.     

Functional properties of palmaris longus muscles of rhesus monkeys transplanted as index finger flexors

This experiment with skeletal muscle autografts in monkeys was designed to retest previous findings that transplanted skeletal muscle can regenerate to a functional degree in primates without predenervation and to test a new hypothesis that increased functional demands on regenerated muscle grafts in monkeys may result in improved functional capacity of the grafts. Rhesus monkey index flexors were replaced with free palmaris longus muscle autografts with microneural anastomoses between the graft motor nerve and the severed profundus motor nerve. One monkey was taught selective index flexion before grafting and continued with this program after grafting to test the effect of training on the graft. Mature grafts were evaluated for in vivo contractile properties and by histology and histochemistry and were compared with a group of normal Rhesus palmaris longus muscles. The results reconfirm the capacity of nonpredenervated monkey skeletal muscle grafts to regenerate and to achieve some contractile ability and suggest that training of free muscle grafts may enhance recovery of their functional and structural properties.     

The mechanism of action of 4-hydroxynonenal in cell injury

The effect of the C9 ketoaldehyde, 4-hydroxynonenal (HNE), a cytotoxic product of lipid peroxidation, on DNA, RNA and protein synthesis has been investigated in cells in culture. Macromolecular synthesis is powerfully inhibited by this agent which readily enters the lipid-rich membranes and is considerably more toxic than the polar ketoaldehyde, methyl glyoxal (MG). The entry of HNE into membranes lowers their glutathione GSH content. This is associated with an increased lipid peroxidation measured in vitro which is blocked by added GSH or alpha-tocopherol. It is proposed that this latter sequence of events is the underlying cause of the cytopathic effect of HNE in cells in culture.     

The abundance of invertebrate herbivores in relation to the availability of nitrogen in stressed food plants

Summary It has previously been postulated that when plants are stressed by certain changes in patterns of weather they become a better source of food for invertebrate herbivores because this stress causes an increase in the amount of nitrogen available in their tissues for young herbivores feeding on them. And this may cause outbreaks of such phytophagous invertebrates.Evidence is now presented that a similar physiological mechanism appears to operate when a wide variety of apparently unrelated environmental factors impinge on plants or parts of plants in such a way as to perturb their metabolism. A broken branch, lightning strike, fire, nutrient deficiencies or an otherwise adverse site; all may have this effect. With the advent of modern man the available agencies increase and diversify to include pesticides, irradiation and air pollutants.One common metabolic response by plants to all such agents impinging on them seems to be equivalent to that found in senescing plant tissues — the breakdown and mobilization of nitrogen in soluble form away from the senescing/stressed tissues. Young herbivores which chance to feed on such stressed/senescing tissues have a greater and more readily available supply of nitrogen in their food than they would have had if feeding on unstressed plants. As a result many more of them survive, and there is an increase in abundance of their kind. Such increases may be quite localised and short-lived or more widespread and persistent, depending on the extent and duration of the stress experienced by the plants. And in the face of this improved nutrition and survival of the very young, predators and parasites seem to have only a minor influence on subsequent changes in abundance of their herbivorous prey.Another effect of increased mobilization of nitrogen in stressed plants is an increase in the quantity of the seed that they set. This has led to the conclusion that increased abundance of some species of birds at such times is due to a greater supply of seeds as winter food for recent fledglings. But it may be that the increased abundance is due to the synchronous increase in phytophagous insects providing a richer source of protein food for laying hens and growing nestlings.