Regulation of S100A10 Gene Expression

S100A10, a member of the S100 family of Ca2+-binding proteins, is a widely distributed protein involved in many cellular and extracellular processes. The best recognized role of S100A10 is the regulation, via interaction with annexin A2, of plasminogen conversion to plasmin. Plasmin, together with other proteases, induces degradation of the extracellular matrix (ECM), which is an important step in tumor progression. Additionally, S100A10 interacts with 5-hydroxytryptamine 1B (5-HT1B) receptor, which influences neurotransmitter binding and, through that, depressive symptoms. Taking this into account, it is evident that S100A10 expression in the cell should be under strict control. In this work, we summarize available literature data concerning the physiological stimuli and transcription factors that influence S100A10 expression. We also present our original results showing for the first time regulation of S100A10 expression by grainyhead-like 2 transcription factor (GRHL2). By applying in silico analysis, we have found two highly conserved GRHL2 binding sites in the 1st intron of the gene encoding S100A10 protein. Using chromatin immunoprecipitation (ChIP) and luciferase assays, we have shown that GRHL2 directly binds to these sites and that this DNA region can affect transcription of S100A10

Stress-Dependent Changes in the CacyBP/SIP Interacting Protein S100A6 in the Mouse Brain.

The CacyBP/SIP target S100A6 is widely present in the nervous system, and its up-regulation is associated with certain neurodegenerative diseases. Here, we examined the involvement of S100A6 protein in stress responses in mice. Using Western blotting, we observed a marked change in brainstem structures, whereby stressed mice showed approximately one-third the protein level produced in the control group. A decreased level of S100A6 protein in stressed animals was also detected in the olfactory bulb and the cerebellum and stress-related structures such as the hippocampus and the hypothalamus. Additionally, using immunohistochemistry, high levels of S100A6 expression were observed in astrocytes localized in the border zones of all brain ventricles, tanycytes of the ventro-lateral walls of the hypothalamus, including the arcuate nucleus (ARH) and low levels of this protein were in neurons of the olfactory bulb, the hippocampus, the thalamus, the cerebral cortex, the brainstem and the cerebellum. Although S100A6-expressing cells in all these brain structures did not change their phenotype in response to stress, the intensity of immunofluorescent labeling in all studied structures was lower in stressed mice than in control animals. For example, in the ARH, where extremely strong immunostaining was observed, the number of immunolabeled fibers was decreased by approximately half in the stressed group compared with the controls. Although these results are descriptive and do not give clue about functional role of S100A6 in stress, they indicate that the level of S100A6 decreases in several brain structures in response to chronic mild stress, suggesting that this protein may modify stress responses

Urinary Bisphenol A Concentrations and Parameters of Ovarian Reserve among Women from a Fertility Clinic

Background: Human exposure to environmentally widespread endocrine disruptors, especially bisphenol A (BPA), has been suggested to affect reproductive health. Animal studies indicate that BPA may play a role in the process of reproduction and impact on maturing oocytes, meiotic cell division or fertilization rate. Nevertheless, data regarding the effects of exposure to BPA on women’s ovarian function are still limited. Therefore, the aim of the current study is to assess the effects of environmental exposure to BPA on ovarian reserve. Methods: The study participants consisted of 511 women in reproductive age (25–39 years) who attended an infertility clinic for diagnosis, due to the couples’ infertility. BPA urinary concentrations were assessed by the validated gas chromatography ion-trap mass spectrometry method. The ovarian reserve was assessed using ovarian reserve parameters: Hormones concentrations: E2 (estradiol), FSH (follicle stimulating hormone), AMH (anti-Müllerian hormone), and AFC (antral follicle count). Results: In the present study, the negative association between BPA urinary concentrations and AMH (p = 0.02) and AFC (p = 0.03) levels was found. Exposure to BPA was not related to other examined parameters of ovarian reserve (FSH, E2). Conclusions: Our results suggest that BPA exposure may affect women ovarian reserve parameters and reduce ovarian reserve. As this is one of the first studies of its kind, the findings need confirmation in a further investigation

Confocal images of brain sections immunostained with S100A6 and vimentin antibodies.

<p>(A, B) the coronal section of the ARH stained for S100A6 (red) and vimentin (green). (D, E) the coronal section of the inferior cerebellar peduncle labeled with S100A6 (red) and vimentin (green). (C, F) merged images. Scale bar equals 50 μ.</p

S100A6-immunoreactivity in mouse brain structures.

<p>(A, B) Coronal sections from anterior and caudal regions of the brain. (C-F) High-magnification images showing S100A6 immunolabeling in the zone close to the dorsal 3rd ventricle (D3V), the corpus callosum (cc), the cerebellum and the pyramidal tract (py). MD—medial dorsal nucleus, AD—anterodorsal nucleus, LD—lateral dorsal nucleus, LV—lateral ventricle, Cpu—caudate-putamen, GP—globus pallidus, Ce—central amygdaloid nucleus, BL—basal amygdaloid nucleus, LH—lateral hypothalamic area, PaV—paraventricular hypothalamic nucleus, AH—anterior hypothalamus, Mve—medial vestibular nucleus, 3V—3rd ventricle, 4V—4th ventricle, ec—external capsule, ic—internal capsule, opt—optic tract, fi—fimbria of hippocampus, st—stria terminalis, sp5- spinal trigeminal tract, icp—inferior cerebellar peduncle, mlf—medial longitudinal fasciculus.</p

Confocal images presenting the phenotypes of S100A6-immunopositive cells in the SVZ.

<p>(A, D, G, J) confocal analysis with anti-S100A6 antibody (red) and (B) anti-GFAP (astrocytic marker, green), (E) anti-Olig2 (oligodendrocytic marker, green), (H) anti-NeuN (neuronal marker, green), (K) anti-MAP2 (dendritic marker, green); (C, F, I, L) merged images.</p

Representative immunofluorescence images for S100A6 in some brain structures related to stress responses.

<p>Immunostained images for S100A6 in the ARH, cerebral cortex and amygdala of control (A-C) and stressed mice (D-F). Scale bars equal 50 μ.</p

Confocal images of the SVZ and the DG.

<p>Sections were stained with antibodies specific for S100A6 (red) and SOX2 (progenitor cell marker, green). (C, F) merged images. Note that a majority of S100A6-labeled cells colocalize with SOX2 in the DG, indicating that S100A6 is expressed in progenitor cells of the DG (F), while weak colocalization between S100A6 and SOX2 in the SVZ (C) is seen.</p

Representative immunofluorescence images for S100A6 in brainstem structures in control and stressed mice.

<p>(A, C) the pyramidal tract in control and stressed mice, (B, D) the spinal trigeminal tract. Scale bar equals 50 μ.</p