Translation in vitro of carnation mottle virus RNA Regulatory function of the 3′-region

Carnation mottle virus (CarMV) RNA was translated in a wheat-germ, cell-free system into three discrete polypeptide chains of 77,000 (CP-I), 38,000 (CP-II) and 30,000 M_r (CPIII). The size of the three polypeptide products represents the translation of almost the entire length of the viral RNA. The CP-II in vitro product was identified as the viral coat protein by gel electrophoresis under denaturing conditions, inununoprecipitation with antibodies directed against the disrupted viral particles, and by peptide mapping. The discrete nature of the three proteins was shown by peptide analysis of the proteolytic products, the absence of cross-reaction between antibodies against CarMV-disrupted particles and CP-I or possibly CP-III, and by the order of their appearance during in vitro translation. Limited phosphorolysis of the 3′-terminus of the viral RNA chains by Escherichia coli polynucleotide phosphorylase caused the selective disappearance of the 77,000 protein product, paralleled with a gradual loss of infectivity. These observations might indicate that the viral RNA is polycistronic, and suggest that the structure at the 3′-terminus of the carnation mottle virus RNA may have a regulatory role in the translation of the viral RNA chains.     

Selective decline in differentiating capacity of immunohemopoietic stem cells with aging

Bone marrow (BM) from young (3 months) and old (24 months) C57BL/6J mice were tested for the total number of colony forming units, which remain unchanged with age. The BM from both groups was used to reconstitute syngeneic, lethally irradiated mice that were 3 months' old. The reconstituted mice were followed for a period of 12 months for their ability to generate cell-mediated responses in mixed lymphocytic cultures and cultures containing the T mitogens--concanavalin A and phytohemagglutinin. For the first 8 months, mice given BM from young or old mice responded to a similar degree. Later, cellular immune responses of the mice reconstituted with BM from old mice declined markedly compared to those reconstituted with BM from young mice, although there was no detectable difference between the two groups in the hematopoietic compartment.     

Vasoactive intestinal peptide receptors: a molecular target in breast and lung cancer

Vasoactive intestinal peptide (VIP) receptors are present in the normal brain as well as periphery, and cancer cells. Three major types of VIP receptors include the VPAC(1), VPAC(2) and PAC(1) receptors. VPAC(1) receptors are present in high densities on human lung and breast cancer cells lines and biopsy specimens. Radiolabeled VIP analogues have been developed for imaging of lung and breast cancer. Synthetic VIP receptor antagonists inhibit the proliferation and potentiate the ability of chemotherapeutic agents to cause apoptosis of lung and breast cancer cells. VIP-chemotherapeutic conjugates have been synthesized which bind to VPAC(1) receptors and are internalized, resulting in the killing of lung and breast cancer cells. These results suggest that VPAC(1) receptors may be molecular targets for diagnosis, prevention and treatment of breast cancer as well as lung cancer.     

Recombinant activity-dependent neuroprotective protein protects cells against oxidative stress

Activity-dependent neuroprotective protein (ADNP) is essential for brain formation. Here, we investigated the potential neuroprotective effects of recombinant ADNP under stress conditions. The human ADNP cDNA was sub-cloned into a vector that contains VP22, a Herpes virus protein that may allow penetration of fused proteins through cellular membranes. When incubated with pheochromocytoma (PC12) cells, a neuronal model, VP22-ADNP was associated with the cells after a 25-min incubation period. Pre-incubation with VP22-ADNP enriched protein fractions protected against beta amyloid peptide toxicity and oxidative stress (H2O2) in PC12 cells. VP22 by itself was devoid of protective activity. Furthermore, the pro-apoptotic protein p53 increased by 3.5-fold from control levels in the presence of H2O2, while treatment with VP22-ADNP prior to H2O2 exposure significantly reduced the p53 protein levels. ADNP expression was previously shown to oscillate as a function of the estrus cycle in the mouse arcuate nucleus, these oscillations are now correlated with increased cellular protection.     

Clinical endocrinology and metabolism. Potential clinical applications of vasoactive intestinal peptide: a selected update

Neuropeptides are expressed in neurons innervating endocrine cells or in endocrine cells and cancer cells, and are released on site to act as hormones and growth factors. Vasoactive intestinal peptide (VIP) was first discovered in the early 1970s and has since become the area of research for many laboratories. VIP has a neuroendocrine role as it is intimately involved with the synthesis, secretion and action of other neuroendocrine hormones as well as cytokines and chemokines. Major outcomes of VIP downregulation encompass developmental and behavioral dysfunctions, including impaired diurnal rhythms. Overexpression of VIP has been associated with diarrhea and cancer, and overexpression of VIP receptors is associated with cancerous growth. This short review outlines some of the recent progress made in VIP research.     

Neuropeptides as growth and differentiation factors in general and VIP in particular

During the course of neurodevelopment a large population of neurons die normally (Berg, 1982; Oppenheim et al., 1989). Are neuropeptides involved in the regulation of neuronal survival, maturation, and maintenance? The peptides are an ever growing family of neuroactive agents and this review shall emphasize VIP (vasoactive intestinal peptide [Said and Mutt, 1970; Gozes and Brenneman, 1989]), which has been shown to be involved in maturation, growth, and maintenance of neurons (Brenneman et al., 1985a, 1987, 1988, 1990, 1990b; Brenneman and Eiden, 1986; Brenneman and Nelson, 1986). Comparative actions of other neuropeptides will also be discussed.