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Calcium signaling mechanisms in alveolar epithelial cells : Effects of physiological and patho-physiological perturbations

Calcium signaling mechanisms in alveolar epithelial cells : Effects of physiological and patho-physiological perturbations

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USMANI, Shariq M., 2011. Calcium signaling mechanisms in alveolar epithelial cells : Effects of physiological and patho-physiological perturbations

@phdthesis{Usmani2011Calci-13597, title={Calcium signaling mechanisms in alveolar epithelial cells : Effects of physiological and patho-physiological perturbations}, year={2011}, author={Usmani, Shariq M.}, note={Teilw. ersch. in:
1: Hecht E, Usmani SM, Albrecht S, Wittekindt OH, Dietl P, Mizaikoff B, Kranz C. Atomic force microscopy of microvillous cell surface dynamics at fixed and living alveolar type II cells. Anal Bioanal Chem. 2011 Mar;399(7):2369-78. PubMed PMID: 21116619.

2: Usmani SM, Fois G, Albrecht S, von Aulock S, Dietl P, Wittekindt OH. 2-APB and capsazepine-induced Ca2+ influx stimulates clathrin-dependent endocytosis in alveolar epithelial cells. Cell Physiol Biochem. 2010;25(1):91-102. Epub 2009 Dec 22. PubMed PMID: 20054148.

3: Albrecht S, Usmani SM, Dietl P, Wittekindt OH. Plasma membrane trafficking in alveolar type II cells. Cell Physiol Biochem. 2010;25(1):81-90. Epub 2009 Dec 22. PubMed PMID: 20054147.}, address={Konstanz}, school={Universität Konstanz} }

2011-06-21T09:49:58Z Kalziumsignalmechanismen in Alveolarepithelzellen : Auswirkung physiologischer und pathophysiologischer Bedingungen Usmani, Shariq M. Calcium signaling mechanisms in alveolar epithelial cells : Effects of physiological and patho-physiological perturbations eng deposit-license 2012-02-16T23:25:04Z The Lung is an important organ of the body which performs the function of gas exchange and maintenance of homeostasis. To do this function lungs are endowed with an extremely large surface which is exposed to the environment and is prone to environmental influences as well as pathogen.<br /><br />Alveoli are the smallest and the most important part of respiratory system, the alveolar epithelium is composed of alveolar epithelial type I and type II (ATII) cells. ATII cells, account for about 95% of the alveolar cell population and perform many of the essential functions in the alveolus such as surfactant exocytosis and maintenance of a thin layer of surfactant on alveolar epithelial surface by endocytosis. Ca<sup>2+</sup> signaling plays a crucial role in ATII cell functioning. Therefore, the aim of this work was to characterize the complex Ca<sup>2+</sup> signaling mechanisms in ATII cells and to investigate cellular processes which are regulated by specific Ca<sup>2+</sup> signaling pathways.<br /><br />In this study, we showed that the Ca<sup>2+</sup> channel modulators 2- Aminoethoxydiphenyl-borinate and capsazepine, activated a Ca<sup>2+</sup> signaling pathway which, in turn activated clathrin -dependent endocytosis. Further experiments showed that the endocytosis mediated a reversible and synchronized internalization of microvilli from the cell surface. This process was associated with the restructuring of cytoskeletal components.<br /><br />ATP activates purinergic receptors resulting in an increased intracellular calcium ([Ca<sup>2+</sup>]<sub>c</sub>) that activates release of surfactant from ATII cells. Unlike the Ca<sup>2+</sup> signaling triggered by 2-APB and capsazepine, purinergic stimulation with ATP activated an endocytic process which was independent of both clathrin and caveolin pathways.<br /><br />In addition to the pharmacological activation of intracellular Ca<sup>2+</sup> signaling, we also showed that the exotoxin from Streptococcus pyogenes, streptolysin O (SLO), can trigger a complex Ca2+ signaling. SLO is a toxin which forms pores in the cell membranes of target cells by oligomerization. Previously, it was assumed that the formation of toxin pores results in a strong Ca<sup>2+</sup> influx into the cell and ultimately causes cell damage. Our results challenge the existing notion, and show that SLO-induced signaling can take place independently of toxin pore; and that intracellular Ca<sup>2+</sup> stores play an essential role in SLO-activated Ca<sup>2+</sup> signaling. In this study, we showed for the first time that intracellular Ca<sup>2+</sup> stores play an important role in SLO-activated Ca<sup>2+</sup> signaling and activate STIM1 and Orai1 proteins mediated store operated Ca<sup>2+</sup> (SOC) entry. We also showed that SOC entry forms the basis of early host response to SLO and results in inflammatory reaction in the epithelial cells.<br /><br />Among other important observations, this work showed that physiological and patho-physiological outcomes can be distinguished on the basis of underlying Ca2+ signaling. Our results show that physiologically Ca<sup>2+</sup> signaling plays an important role in regulating endocytic processes in alveolar epithelial cells through different pathways. On the other hand, bacterial toxin streptolysin O, which at the concentrations used in our study represents an early stage of a streptococcal infection, induced a Ca<sup>2+</sup> signaling pathway which resulted in pro-inflammatory response.<br /> 2011 Usmani, Shariq M.

Dateiabrufe seit 01.10.2014 (Informationen über die Zugriffsstatistik)

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