Thesis (Ph.D.)--Hong Kong University of Science and Technology, 2006. / Includes bibliographical references (leaves 126-135). Also available in electronic version.

Thesis (Ph. D.)--University of Queensland, 2001. / Includes bibliographical references.

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

Aberrant phenotypes of airway smooth muscle cells are central to the pathophysiology of asthma. The hypercontractile nature of these cells and hypertrophy are the key reasons for the excessive narrowing of the airways observed in allergic asthma. Although previous studies have indicated a role of enhanced content of smMLCK in modulating the contractile reactivity, as well as an indication of hypertrophy of HASM cells in asthmatic conditions, the effect of IgE on the expression of smMLCK in HASM cells is not fully understood. In this study, we demonstrate that IgE augments the expression of smMLCK at the mRNA and protein level. Inhibition of IgE binding with anti-FcεRI blocking antibody, Syk silencing, pharmacological inhibitors to MAPK (ERK1/2, p38, and JNK) and PI3K significantly diminished the IgE-mediated smMLCK expression in HASM cells. Finally, we found that IgE, similar to metacholine induces the contraction of HASM cells grown on collagen gel matrix. Our data suggest that IgE stimulates the phosphorylation of ERK, P38, STAT3 and induces the dephosphorylation of smMLCK to phosphorylate myosin regulatory light chain in HASM cells. Taken together, our data suggest a modulatory role of IgE in regulating the contractile machinery and hypertrophic phenotype of HASM cells.

No description available.

Aberrant phenotypes of airway smooth muscle cells are central to the pathophysiology of asthma. The hypercontractile nature of these cells and hypertrophy are the key reasons for the excessive narrowing of the airways observed in allergic asthma. Although previous studies have indicated a role of enhanced content of smMLCK in modulating the contractile reactivity, as well as an indication of hypertrophy of HASM cells in asthmatic conditions, the effect of IgE on the expression of smMLCK in HASM cells is not fully understood. In this study, we demonstrate that IgE augments the expression of smMLCK at the mRNA and protein level. Inhibition of IgE binding with anti-FcεRI blocking antibody, Syk silencing, pharmacological inhibitors to MAPK (ERK1/2, p38, and JNK) and PI3K significantly diminished the IgE-mediated smMLCK expression in HASM cells. Finally, we found that IgE, similar to metacholine induces the contraction of HASM cells grown on collagen gel matrix. Our data suggest that IgE stimulates the phosphorylation of ERK, P38, STAT3 and induces the dephosphorylation of smMLCK to phosphorylate myosin regulatory light chain in HASM cells. Taken together, our data suggest a modulatory role of IgE in regulating the contractile machinery and hypertrophic phenotype of HASM cells.

ClC-1 is the major skeletal muscle chloride channel and is essential for re-establishing the resting membrane potential of muscle cells after an action potential has occurred. Many mutations throughout the CLCN1 gene, which codes for the CIC-1 protein, have been demonstrated via characterisation in heterologous expression systems, to be causative mutations for either Dominant Myotonia Congenita or Recessive Generalised Myotonia. Recently, increasing numbers of myotonic mutations have been found in the carboxyl tail of CIC-1, which demonstrates its importance as a domain that is essential for the normal function of CIC-1 channels. Previous studies in our laboratory defined a region of 18 amino acids in the immediate post D13 segment of rat CIC-1, essential for the expression of functional channels. / Thesis (PhDBiomedicalScience)--University of South Australia, 2002.

ClC-1 is the major skeletal muscle chloride channel and is essential for re-establishing the resting membrane potential of muscle cells after an action potential has occurred. Many mutations throughout the CLCN1 gene, which codes for the CIC-1 protein, have been demonstrated via characterisation in heterologous expression systems, to be causative mutations for either Dominant Myotonia Congenita or Recessive Generalised Myotonia. Recently, increasing numbers of myotonic mutations have been found in the carboxyl tail of CIC-1, which demonstrates its importance as a domain that is essential for the normal function of CIC-1 channels. Previous studies in our laboratory defined a region of 18 amino acids in the immediate post D13 segment of rat CIC-1, essential for the expression of functional channels. / thesis (PhDBiomedicalScience)--University of South Australia, 2002.

Thesis (M.Sc.)--York University, 1999. Graduate Programme in Kinesiology and Health Science. / Typescript. Includes bibliographical references (leaves 77-79). Also available on the Internet. MODE OF ACCESS via web browser by entering the following URL: http://wwwlib.umi.com/cr/yorku/fullcit?pMQ56210

Thesis (Ph.D.)--York University, 2007. Graduate Programme in Biology. / Typescript. Includes bibliographical references. Also available on the Internet. MODE OF ACCESS via web browser by entering the following URL: http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&res_dat=xri:pqdiss&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&rft_dat=xri:pqdiss:NR32052