Biomedical subjects

Tanja Maritzen

Publications and source records attributed to Tanja Maritzen.

4 recordsLinked to original sources

PubMed2006

Neurogenic mechanisms contribute to hypertension in mice with disruption of the K-Cl cotransporter KCC3.

The neurodegenerative disorder Andermann syndrome is caused by mutations of the K-Cl cotransporter KCC3. Mice with a targeted disruption of the corresponding gene, Slc12a6, reproduce neurodegeneration of the peripheral and central nervous system (CNS) and display arterial hypertension. Kcc3 is expressed in numerous tissues, including the CNS and vascular smooth muscle cells. As the intracellular chloride concentration may influence myogenic tone and hence blood pressure, we measured the chloride concentration in vascular smooth muscle cells. It was indeed increased in superficial brain arteries and saphenous arteries of Kcc3(-/-) mice. Isolated saphenous arteries and their third-order branches, however, reacted indistinguishably to changes in intravascular pressure, stimulation of alpha1-adrenoreceptors, exogenous nitric oxide, or blockade of calcium-activated chloride channels. Likewise, the responses to alpha1-adrenergic stimulation or exogenous nitric oxide in vivo were identical in both genotypes. These results argue against a major vascular-intrinsic component of arterial hypertension in Kcc3(-/-) mice. In contrast, either alpha1-adrenergic blockade or inhibition of ganglionic transmission abolished the difference in arterial blood pressure between both genotypes. This demonstrates a neurogenic component in the maintenance of this phenotype, which is further supported by an increase of urinary norepinephrine and epinephrine excretion in Kcc3(-/-) mice. Our data indicate that local control of myogenic tone does not require KCC3 and that hypertension in Kcc3(-/-) mice depends on an elevated sympathetic tone.

Aldosterone↗

PubMed2006

ClC-5 does not affect megalin expression and function in the thyroid.

Megalin is an endocytic receptor responsible for thyroglobulin (Tg) transcytosis, a process that favors hormone release. Accordingly, megalin KO mice have primary hypothyroidism. In the kidney, megalin expression is reduced when the gene encoding the chloride transporter ClC-5 is mutated. We investigated whether megalin expression and function in the thyroid are affected by ClC-5 using a ClC-5 KO mouse model. By Western blotting, ClC-5 was found in thyroid tissue extracts of WT, but not of ClC-5 KO mice. In addition, ClC-5 was found to be expressed by cultured thyroid cells (FRTL-5). The thyroid size, weight, and histology were similar in ClC- 5 KO and WT mice, as were the amounts of megalin in thyroid extracts. Accordingly, serum Tg, a measure of megalin-mediated transcytosis, was similar in WT and ClC-5 KO mice, suggesting that megalin function was unaffected. Thus, unlike in megalin KO mice, in ClC-5 KO mice thyroid function was unchanged, as indicated by the normal serum FT4 and TSH. We concluded that in the thyroid, unlike in the kidney, ClC-5 does not affect megalin expression and function, suggesting that megalin is differentially regulated in these two organs.

Animals↗

PubMed2005

Chloride channel diseases resulting from impaired transepithelial transport or vesicular function.

The transport of anions across cellular membranes is crucial for various functions, including the control of electrical excitability of muscle and nerve, transport of salt and water across epithelia, and the regulation of cell volume or the acidification and ionic homeostasis of intracellular organelles. Given this broad range of functions, it is perhaps not surprising that mutations in Cl- channels lead to a large spectrum of diseases. These diverse pathologies include the muscle disorder myotonia, cystic fibrosis, renal salt loss in Bartter syndrome, kidney stones, deafness, and the bone disease osteopetrosis. This review will focus on diseases related to transepithelial transport and on disorders involving vesicular Cl- channels.

Animals↗

PubMed2003

Casein kinase I delta (CKIdelta) is involved in lymphocyte physiology.

The casein kinase I isoform delta (CKIdelta) plays an important role in vesicular trafficking, chromosome segregation, cell cycle progression, cytokinesis, developmental processes, and circadian rhythm. In this study we examined the distribution pattern of CKIdelta and quantified its kinase activity in various tissues of BALB/c mice. Whereas CKIdelta is ubiquitously expressed, differences in the kinase activity were detected in organs with comparable CKIdelta protein levels. To elucidate the role of CKIdelta in splenocytes, which displayed the highest kinase activity, the cell type-specific distribution of CKIdelta within the spleen was investigated. Immunohistochemical analysis revealed a strong CKIdelta immunolabeling in lymphoid cells of the white pulp, while in the red pulp CKIdelta immunoreactivity was found in cells of various haematopoietic lineages. Furthermore, high CKIdelta kinase acitivity was observed in isolated lymphocytes and granulocytes of young BALB/c mice. In lymphocytes the CKIdelta activity increased upon mitogenic stimulation, whereas upon gamma-irradiation CKIdelta protein and activity levels were diminished. Interestingly, the comparison of CKIdelta activity in p53+/+ and p53-/- lymphocytes revealed a higher activity in p53+/+ lymphocytes. In addition, we observed an increased immunostaining in cells of hyperplastic B follicles and advanced B-cell lymphomas in p53-deficient mice. Thus, our results indicate that CKIdelta plays several roles in lymphocyte physiology.

Animals↗