ABSTRACT
Endothelial cells produce nitric oxide (NO), a potent vasodilator. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of NO synthase. Little is known about the potential physiological roles of ADMA in a perinatal setting. This study measures concentrations of ADMA in umbilical blood using enzyme-linked immunosorbent assay and those of NO as nitrite/nitrate (NOx(-)) using the Griess assay. Their relationship to the degree of prematurity and maternal clinical condition is examined. Results show that ADMA concentrations in umbilical blood from control newborns were about twice as high as those of lactating women, healthy children, and healthy adults. Umbilical blood NOx(-) concentrations from control newborns were about half of those of lactating women, healthy children, and healthy adults. Consequently, the levels of ADMA relative to NOx(-) were about 4-fold higher in umbilical blood from control newborns than in blood from lactating women, healthy children, and healthy adults. Furthermore, the umbilical blood ADMA concentrations and the ratios of ADMA to NOx(-) in newborns were higher according to their birth prematurity and lower birth weight. The umbilical ADMA concentrations were independent of the delivery mode and maternal preeclampsia. We infer that the high ADMA levels play physiological roles in maintaining vascular tone and blood redistribution to vital organs during birth, thereby favoring the circulatory transition from fetal to neonatal life.
Subject(s)
Arginine/analogs & derivatives , Enzyme Inhibitors/blood , Fetal Blood/chemistry , Nitric Oxide Synthase Type III/antagonists & inhibitors , Adolescent , Adult , Arginine/blood , Child , Child, Preschool , Female , Humans , Infant, Newborn , Infant, Premature , Linear Models , Male , Middle Aged , Nitrates/blood , Nitrites/blood , Pregnancy , Umbilical VeinsABSTRACT
The maturation/lysis (A2) protein encoded by the group B single-stranded RNA bacteriophage Qbeta mediates lysis of host Escherichia coli cells. We found a frameshift mutation in the replicase (beta-subunit) gene of Qbeta cDNA causes cell lysis. The mutant has a single base deletion 73 nucleotides (nt) 3' from the start of the replicase gene with consequent translation termination at a stop codon 129-131 nt further 3'. The 43-amino acid C-terminal part of the 67-amino acid product encoded by what in WT (wild-type) is the +1 frame, is rich in basic amino acids This 67-aa protein can mediate cell lysis whose characteristics indicate that the protein may cause lysis by a different mechanism and via a different target, than that caused by the A2 maturation/lysis protein. Synthesis of a counterpart of the newly discovered lysis product in wild-type phage infection would require a hypothetical ribosomal frameshifting event. The lysis gene of group A RNA phages is also short, 75 codons in MS2, and partially overlaps the first part of their equivalently located replicase gene, raising significant evolutionary implications for the present finding.
