Naltrexone partially inhibits the estrogen-induced increase in prolactin secretion and anterior pituitary weight

The effects of naltrexone, a specific opiate antagonist, on stimulation by estradiol benzoate (EB) of prolactin (PRL) release and anterior pituitary (AP) weight, were studied in gonadectomized female and male Sprague-Dawley rats. One week after castration, rats were injected for 10 days once daily with 2 μg EB alone, or together with twice daily injections of 2 mg naltrexone/kg body weight (BW). Blood was collected for radioimmunoassay of PRL by orbital sinus puncture on days 0 and 6, and by decapitation on day 11, at which time the AP was quickly removed, weighed and assayed for PRL.Serum PRL concentrations and AP weights were significantly increased by EB administration. These effects of EB were partially but significantly inhibited by naltrexone. These results suggest that endegenous opiates may be involved in the estrogen-induced rise in serum PRL and increase in pituatary weight.     

Conformational transitions of uracil transporter UraA from Escherichia coli: a molecular simulation study

The Escherichia coli uracil/H + symporter UraA, known as the representative nucleobase/cation symporter 2(NCS2) protein, gets involved in several crucial physiological processes for most living organisms on Earth, such as the uptake of nucleobases and transport of vitamin C. Some experiments proposed a working model to explain proton-coupling and uracil transporting process of UraA on the basis of the crystal structure of NCS2 protein, but the details of conformational changes remained unknown. Thus, in order to make clear conformational changes caused by the protonation and deprotonation process of some conserved proton-coupled residues, the molecular dynamics simulation was used to study the conformation of UraA complexes in different protonation states. The results demonstrated that the protonation of residue Glu241 and Glu290 resulted in the whole conformational transition from the inward-open to the outward-open state. It can be concluded that Glu290 was crucial in a network of hydrogen-bonds in the middle of the core domain involving another essential residue, mainly including tyr288 in TM8, Tyr342, Ser338 in TM12, and the network of hydrogen-bonds was the key to maintain the stability of conformation. Protonation of Glu290 affects the stability of network of H-bond and changed the domains TM3 TM10 TM12. Thus, Glu290 may play a vital role as a ‘proton trigger’ that affects spatial structural of amino and residues near substrate binding side leading to an outward-open conformation transition.     

Composition and function of the eukaryotic N-terminal acetyltransferase subunits

Saccharomyces cerevisiae contains three N-terminal acetyltransferases (NATs), NatA, NatB, and NatC, composed of the following catalytic and auxiliary subunits: Ard1p and Nat1p (NatA); Nat3p and Mdm20p (NatB); and Mak3p, Mak10, and Mak31p (NatC). The overall patterns of N-terminally acetylated proteins and NAT orthologous genes suggest that yeast and higher eukaryotes have similar systems for N-terminal acetylation. The differential expression of certain NAT subunits during development or in carcinomas of higher eukaryotes suggests that the NATs are more highly expressed in cells undergoing rapid protein synthesis. Although Mak3p is functionally the same in yeast and plants, findings with TE2 (a human Ard1p ortholog) and Tbdn100 (a mouse Nat1p ortholog) suggest that certain of the NAT subunits may have functions other than their role in NATs or that these orthologs are not functionally equivalent. Thus, the vertebrate NATs remain to be definitively identified, and, furthermore, it remains to be seen if any of the yeast NATs contribute to other functions.     

Polymorphisms in the N acetyltransferase 1 NAT1 gene and lung cancer risk in a minority population

One of the most consistently observed exposure-disease relationship is the one between cigarette smoking and lung cancer. Aromatic amines and their metabolites are found in tobacco smoke and may be a class of carcinogen involved in lung carcinogenesis. T he human N -acetyltransferase 1 ( NAT 1 ) enzyme can activate or deactivate aromatic amines, making it a candidate genetic susceptibility gene. We evaluated the potential role of the NAT 1 gene in lung cancer risk in a hospital-based case-control study in a minority population composed of Mexican- and African-Americans. We also assessed the potential interaction between NAT 1 and other environmental exposures such as cigarette smoking. T here was no overall association between the NAT1*10 genotypes and lung cancer risk. T he adjusted odds ratio for the rapid acetylation genotypes was 0 72 (95 % CI 0 37-1 39) for NAT1 defined as the presence of at least one copy of the NAT1*10 allele when compared with all genotypes without the NAT1*10 allele. Analyses by histological subtype or smoking history did not alter these findings. Other NAT 1 alleles will need to be studied for more conclusive results regarding the relevance of NAT 1 activity to lung carcinogenesis.     

N-terminal modifications contribute to flowering time and immune response regulations

A variety of N-terminal co-translational modifications play crucial roles in many cellular processes across eukaryotic organisms. Recently, N-terminal acetylation has been proposed as a regulatory mechanism for the control of plant immunity. Analysis of an N-terminal acetyltransferase complex A (NatA) mutant, naa15–1, revealed that NatA controls the stability of immune receptor Suppressor of NPR1, Constitutive 1 (SNC1) in an antagonistic fashion with NatB. Here, we further report on an antagonistic regulation of flowering time by NatA and NatB, where naa15–1 plants exhibit late flowering, opposite of the early flowering phenotype previously observed in natB mutants. In addition, we provide evidence for the involvement of another N-terminal modification, N-myristoylation, in controlling pathogen-associated molecular pattern (PAMP) triggered immunity (PTI) through the characterization of N-myristoyltransferase 1 (NMT1) defective mutants, which express a low level of NMT1 protein. The mutant line lacks induced production of reactive oxygen species and MAP kinase phosphorylation in response to treatment with the known immune elicitor flg22. NMT1 deficient plants also exhibit increased susceptibility to Pst hrcC, a non-pathogenic Pseudomonas syringae tomato strain lacking a functional type-III secretion system. The potential for the NatA-NatB antagonistic relationship to exist outside of the regulation of SNC1 as well as the disclosing of NMT1s role in PTI further supports the significant contribution of N-terminal co-translational modifications in the regulation of biological processes in plants, and present interesting areas for further exploration.