Biomedical subjects

V M Perreau

Publications and source records attributed to V M Perreau.

6 recordsLinked to original sources

PubMed2006

Melatonin treatment in old mice enables a more youthful response to LPS in the brain.

Melatonin modulates the expression of a number of genes related to inflammation and immunity. Declining levels of melatonin with age may thus relate to some of the changes in immune function that occur with age. mRNA expression levels in murine CNS were measured using oligonucleotide microarrays in order to determine whether a dietary melatonin supplement may modify age-related changes in the response to an inflammatory challenge. CB6F1 male mice were fed 40-ppm melatonin for 9 weeks prior to sacrifice at 26.5 months of age, and compared with age-matched untreated controls and 4.5-month-old controls. A subset of both young and old animals was injected i.p. with lipopolysaccharide (LPS). After 3 h, total RNA was extracted from whole brain (excluding brain stem and cerebellum), and individual samples were hybridized to Affymetrix Mouse 430-2.0 arrays. Data were analyzed in Dchip and GeneSpring. Melatonin treatment markedly altered the response in gene expression of older animals subjected to an LPS challenge. These changes in general, caused the response to more closely resemble that of young animals subjected to the same LPS challenge. Thus melatonin treatment effects a major shift in the response of the CNS to an inflammatory challenge, causing a transition to a more youthful mRNA expression profile.

Aging↗

PubMed2004

Retardation of brain aging by chronic treatment with melatonin.

Slowing the functional decline in the aging brain is not only relevant to nonpathological senescence but also to a broad range of neurodegenerative diseases. Although disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD) are not found in the young adult, they gradually manifest with increasing age. AD, in particular, is an increasing major public health concern as the population ages; therapies that delay disease onset will markedly reduce overall disease prevalence. Aging of the brain has been repeatedly associated with cumulative oxidative damage to macromolecules and to abnormal levels of inflammatory activity. Melatonin has attained increasing prominence as a candidate for ameliorating these changes occurring during senescence. Recent research has focused on supplementation with dietary melatonin designed to elucidate the specific key intracellular targets of age-related inflammatory events, and the optimal means of affording protection of these targets. This report summarizes the progress made in this area.

Aging↗

PubMed2001

Effects of exercise on gene-expression profile in the rat hippocampus.

Exercise has beneficial effects on brain function, including the promotion of plasticity and the enhancement of learning and memory performance. Previously we found that exercise increases the expression of certain neurotrophic factors including brain derived neurotrophic factor in the rat hippocampus. To further explore the molecular mechanisms underlying these changes, we used high-density oligonucleotide microarrays containing probe sets representing approximately 5000 genes to analyze the level of gene transcripts in the hippocampus of rats voluntary running for 3 weeks in comparison with sedentary animals. An improved statistical approach for the analysis of DNA microarray data, Cyber-T, was utilized in data analysis. Here we show that exercise leads to changes in the level of a large number of gene transcripts, many of which are known to be associated with neuronal activity, synaptic structure, and neuronal plasticity. Our data indicate that exercise elicits a differential gene expression pattern with significant changes in genes of relevance for brain function.

Aging↗

PubMed1999

The Candida albicans CUG-decoding ser-tRNA has an atypical anticodon stem-loop structure.

In many Candida species, the leucine CUG codon is decoded by a tRNA with two unusual properties: it is a ser-tRNA and, uniquely, has guanosine at position 33 (G33). Using a combination of enzymatic (V1 RNase, RnI nuclease) and chemical (Pb(2+), imidazole) probing of the native Candida albicans ser-tRNACAG, we demonstrate that the overall tertiary structure of this tRNA resembles that of a ser-tRNA rather than a leu-tRNA, except within the anticodon arm where there is considerable disruption of the anticodon stem. Using non-modified in vitro transcripts of the C. albicans ser-tRNACAG carrying G, C, U or A at position 33, we demonstrate that it is specifically a G residue at this position that induces the atypical anticodon stem structure. Further quantitative evidence for an unusual structure in the anticodon arm of the G33-tRNA is provided by the observed change in kinetics of methylation of the G at position 37, by purified Escherichia coli m(1)G37 methyltransferase. We conclude that the anticodon arm distortion, induced by a guanosine base at position 33 in the anticodon loop of this novel tRNA, results in reduced decoding ability which has facilitated the evolution of this tRNA without extinction of the species encoding it.

Anticodon↗

PubMed1997

Beta, a novel repetitive DNA element associated with tRNA genes in the pathogenic yeast Candida albicans.

We have identified a novel 399 bp repetitive DNA element (which we designate beta) 9bp upstream of a seryl-tRNA(CAG) gene in the genome of Candida albicans. There are two copies of the seryl-tRNA(CAG) gene, one on each homologue of chromosome VI, and the beta element is found upstream of one copy of the gene in C. albicans strain 2005E. The beta element is not present upstream of either copy of the seryl-tRNA(CAG) gene in eight other laboratory strains of C. albicans tested, but was detected in this location in several fresh clinical isolates. Southern blot analysis indicated that there are approximately eight copies of the beta element per diploid C. albicans genome and that it is a mobile element, being present on at least two different chromosomes. Three unique genomic DNA clones containing the beta element were isolated from strain 2005E; in each case, a different tRNA gene was found immediately adjacent to the beta element. Three new tRNA genes from C. albicans have thus been identified: tRNA(Asp), tRNA(Ala) and tRNA(Ile). The beta element shows no significant sequence homology to other known prokaryotic or eukaryotic repetitive elements, although an 8 bp repeat at the 3' end of the element is identical to that of the Ty3 retrotransposable element of Saccharomyces cerevisiae. We propose that the beta element is a solo long terminal repeat (LTR) sequence of a Ty3/gypsy-like transposable element in C. albicans that is closely associated with tRNA genes.

Base Sequence↗

PubMed1996

Transfer RNA structural change is a key element in the reassignment of the CUG codon in Candida albicans.

The human pathogenic yeast Candida albicans and a number of other Candida species translate the standard leucine CUG codon as serine. This is the latest addition to an increasing number of alterations to the standard genetic code which invalidate the theory that the code is frozen and universal. The unexpected finding that some organisms evolved alternative genetic codes raises two important questions: how have these alternative codes evolved and what evolutionary advantages could they create to allow for their selection? To address these questions in the context of serine CUG translation in C.albicans, we have searched for unique structural features in seryl-tRNA(CAG), which translates the leucine CUG codon as serine, and attempted to reconstruct the early stages of this genetic code switch in the closely related yeast species Saccharomyces cerevisiae. We show that a purine at position 33 (G33) in the C.albicans Ser-tRNA(CAG) anticodon loop, which replaces a conserved pyrimidine found in all other tRNAs, is a key structural element in the reassignment of the CUG codon from leucine to serine in that it decreases the decoding efficiency of the tRNA, thereby allowing cells to survive low level serine CUG translation. Expression of this tRNA in S.cerevisiae induces the stress response which allows cells to acquire thermotolerance. We argue that acquisition of thermotolerance may represent a positive selection for this genetic code change by allowing yeasts to adapt to sudden changes in environmental conditions and therefore colonize new ecological niches.

Base Sequence↗