Brain natriuretic peptide correlates with the extent of atrial fibrillation-associated silent brain lesions.

OBJECTIVE: Identification of plasma markers indicative for atrial fibrillation-associated silent brain lesions. DESIGN AND METHODS: 1. Comparative determination of the plasma concentrations of secretagogin, S100B, neuropeptide Y, brain fatty acid binding protein, matrix metalloprotease 9, brain natriuretic peptide, and of D-Dimer in 222 patients with atrial fibrillation and 28 controls by immunoassays. 2. Correlation of the biochemical marker plasma concentration with the extent of silent white matter brain lesions, as determined by the Fazekas score and N-acetylaspartate-spectroscopy. RESULTS: 1. Plasma concentrations of brain natriuretic peptide, of neuropeptide Y, and of matrix metalloprotease 9 were significantly higher (all with a p<0.05) in patients suffering from atrial fibrillation than in control subjects. 2. Brain natriuretic peptide correlated significantly with the Fazekas score (R=0.41; p<0.005). 3. Brain natriuretic peptide plasma concentrations were significantly higher in patients with a pathological N-acetylaspartate magnetic resonance-spectrometry (p<0.05). CONCLUSION: Brain natriuretic peptide plasma concentrations correlate with the extent of atrial fibrillation-associated silent brain lesions.

Setagin and secretagogin-R22: Posttranscriptional modification products of the secretagogin gene.

We describe two new variants of the recently identified hexa-EF-hand calcium binding protein secretagogin. The first variant (secretagogin-R22) is characterized by one single amino acid exchange (Q/R) at codon 22, most likely due to RNA editing. The second variant of secretagogin (setagin) consists of 49 amino acids. Due to a frame shift, only the first 27 amino acids are identical to secretagogin. We demonstrate that this protein truncation results in complete loss of the calcium binding capacity. Setagin expression was found in considerable amounts in the pancreas whereas secretagogin and secretagogin-R22 were also found in the central nervous system and organs containing neurendocrine cells.

The ATP-dependent helicase RUVBL1/TIP49a associates with tubulin during mitosis.

RUVBL1/TIP49a/Pontin52 is a recently identified multi-functional protein with 2 ATP binding (WALKER) sites, which is essential for cell proliferation. We recovered and identified RUVBL1/TIP49a as a tubulin-binding protein from Triton X-100 lysates of U937 promonocytic cells by protein affinity chromatography and tryptic peptide microsequencing. Performing co-immunoprecipitation using newly generated RUVBL1/TIP49a-specific antibodies (mAb and rabbit polyclonal Ab) and RUVBL1/TIP49a-GST fusion protein-pull down assays we demonstrate co-precipitation of alpha- and gamma tubulin with RUVBL1/TIP49a. Confocal immunoflourescence microscopy reveals that RUVBL1/TIP49a was present not only in the nucleus, as expected, but was also concentrated at the centrosome and at the mitotic spindle in colocalization with tubulin. The topology of RUVBL1/TIP49a at the mitotic spindle varied, depending on the mitotic stage. The protein was localized at the centrosome and at the polar and astral microtubules in metaphase, and was detectable at the zone of polar tubule interdigitation in anaphase B and telophase. During cytokinesis the protein reappeared at the area of decondensing chromosomes. Whereas preincubation of U937 cells with colcemid resulted in inhibition of mitotic spindle formation with subsequent loss of RUVBL1/TIP49a mitotic spindle staining, no relevant influence of colcemid on RUVBL1/TIP49a-tubulin binding was observed. An agonistic effect of RUVBL1/TIP49a on in vitro tubulin assembly is demonstrated. Our results reveal a new functional aspect of RUVBL1/TIP49a.