Biomedical subjects

Ornella Senatori

Publications and source records attributed to Ornella Senatori.

3 recordsLinked to original sources

PubMed2005

Molecular characterization of monoamine oxidase in zebrafish (Danio rerio).

Monoamine oxidase (MAO) is responsible for the degradation of a number of neurotransmitters and other biogenic amines. In terrestrial vertebrates, two forms of the enzyme, named MAO A and B, were found in which mammals are coded by two similar but distinct genes. In teleosts, the biochemical data obtained so far indicate that enzyme activity is due to a single form, whose sequence, obtained for trout, displays 70% identity with mammal MAO A and B. In this paper, we carried out an investigation of zebrafish MAO (Z-MAO) to shed further light on the nature of the MAO form present in aquatic vertebrates. Sequencing studies have revealed an open reading frame 522-amino-acids long with MW 58.7 kDa, displaying 84% identity with trout MAO and about 70% identity with mammal MAO A and MAO B. Analysis of the sequence and of the predicted secondary structure shows that also in Z-MAO principal domains characterizing the MAOs are present. The domain linking the FAD is very well conserved, while the transmembrane domain sequence linking the enzyme to the external mitochondrial membrane does not appear to be conserved even with respect to trout MAO. Comparison with the amino acids which, according to the human MAO B and rat MAO A models, line the substrate-binding site shows that in Z-MAO, several residues (V172, N173, F200, L327) differ from MAO B but are similar or identical to the corresponding ones present in rat MAO A, as well as in trout MAO. A three-dimensional model is reported of the substrate-binding site of Z-MAO obtained by comparative modeling. Our observations support the hypothesis that the MAO form present in aquatic vertebrates is a MAO A-like form. Experiments performed to test the effect of selective MAO A (clorgyline) and MAO B (deprenyl) inhibitors on the enzyme's activity in liver and brain confirm the presence of a single form of MAO in zebrafish.

Amino Acid Sequence↗

PubMed2004

Monoamine oxidase expression during development and aging.

Monoamine oxidase (MAO) isoenzymes play a major role in regulating the concentration of several bioactive amines, including serotonin and catecholamines. Both in the nervous system and in peripheral organs, MAOs can potentially modulate all the processes involving these bioactive amines. In the present article, we review some of the most significant articles published so far on changes in MAOs during development and aging. The data available on development refer mainly to the mammal brain at fetal and post-fetal stages. Very little work has been done on studying MAO ontogenesis during early development, that is, at stages prior to organogenesis, and what has been done refers to non-mammal vertebrates such as fish, amphibians and birds. MAO A and MAO B changes have been measured as values of enzymatic activity, as amount of protein or, more rarely, as amount of mRNAs. A knowledge of MAO developmental changes not only provides a basis for the investigation of factors regulating MAO expression, but can also contribute to a better understanding of the possible trophic and/or morphogenetic role of monoaminergic neurotransmitters in the developing brain. Transgenic mice lacking MAO A and rodents treated with MAO inhibitors during gestation have been very useful in this second case. The investigations of changes in MAO A and MAO B during aging in the literature refer mostly to humans, mice and rats. Interest in studies on aging is stimulated, among other things, by the observation that age-related diseases leading to neurodegenerative phenomena could be accompanied by changes in MAO activity.

Aging↗

PubMed2002

Monoamine oxidase A and B activities in embryonic chick hepatocytes: differential regulation by retinoic acid.

Monoamine oxidases (MAOs) A and B are two isoenzymes involved in the degradation of many biological amines in the nervous system and in peripheral organs. In the present work hepatocytes isolated from 14-day-old chick embryos were used as a model system to determine whether retinoic acid (RA) is capable of modulating the activity of the two MAO forms. RA is a retinoid that, by binding with nuclear receptors, interferes with the expression of specific genes in many differentiation processes. Enzymic activity was measured with a radiochemical method using serotonin and beta-phenylethylamine as preferential substrates for MAO A and MAO B, respectively. The specific activity of the two forms was measured in hepatocytes cultured for 24, 48 and 72 h in the presence and the absence of serum. RA stimulated MAO B but not MAO A activity, in a dose- and time-dependent way, and only in the presence of serum. Maximum stimulation (about 3.5-fold) was obtained after treatment with 5 microM RA for 72 h. Kinetic analysis of MAO B activity showed an increase in V(max) in treated hepatocytes (5 microM RA for 72 h) with no change in K(m). In conclusion, the present work shows that RA selectively elicits MAO B activity in cultured chick embryonic hepatocytes, this stimulation requires the presence of some factors present in the serum and is probably due to an increase in the number of enzyme molecules.

Animals↗