Aromatase expression in the human temporal cortex

13 pages, 8 figures, 2 tables.-- PMID: 16426763 [PubMed].The expression of the human cyp19 gene, encoding P450 aromatase, the key enzyme for estrogen biosynthesis, involves alternative splicing of multiple forms of exon I regulated by different promoters. Aromatase expression has been detected in the human cerebral cortex, although the precise cellular distribution and promoter regulation are not fully characterized. We examined the variants of exon I of cyp19 by PCR analysis and the cellular distribution of the enzyme using immunohistochemistry in the human temporal cortex. We detected four different variants of exon I, suggesting a complex regulation of cyp19 in the cerebral cortex. In addition, the enzyme was localized mainly in a large subpopulation of pyramidal neurons and in a subpopulation of astrocytes. However, the majority of GABAergic interneurons identified by their expression of the calcium-binding proteins calbindin, calretinin and parvalbumin, did not display aromatase immunoreactivity. The broad range of potential modulators of the cyp19 gene in the cortex and the widespread expression of the protein in specific neuronal and glial subpopulations suggest that local estrogen formation may play an important role in human cortical function.This study has been carried out with financial support from Ministerio de Ciencia y Tecnología, Spain (SAF 2002–00652, SAF 2005–00272, BFI2003-02745 and BFI2003-01018).Peer reviewe

Quantitative and integrative proteome analysis of peripheral nerve myelin identifies novel myelin proteins and candidate neuropathy loci

Peripheral nerve myelin facilitates rapid impulse conduction and normal motor and sensory functions. Many aspects of myelin biogenesis, glia-axonal interactions, and nerve homeostasis are poorly understood at the molecular level. We therefore hypothesized that only a fraction of all relevant myelin proteins has been identified so far. Combining gel-based and gel-free proteomic approaches, we identified 545 proteins in purified mouse sciatic nerve myelin, including 36 previously known myelin constituents. By mass spectrometric quantification, the predominant P0, periaxin, and myelin basic protein constitute 21, 16, and 8% of the total myelin protein, respectively, suggesting that their relative abundance was previously misestimated due to technical limitations regarding protein separation and visualization. Focusing on tetraspan-transmembrane proteins, we validated novel myelin constituents using immuno-based methods. Bioinformatic comparison with mRNA-abundance profiles allowed the categorization in functional groups coregulated during myelin biogenesis and maturation. By differential myelin proteome analysis, we found that the abundance of septin 9, the protein affected in hereditary neuralgic amyotrophy, is strongly increased in a novel mouse model of demyelinating neuropathy caused by the loss of prion protein. Finally, the systematic comparison of our compendium with the positions of human disease loci allowed us to identify several candidate genes for hereditary demyelinating neuropathies. These results illustrate how the integration of unbiased proteome, transcriptome, and genome data can contribute to a molecular dissection of the biogenesis, cell biology, metabolism, and pathology of myelin