Modulation by thyroid hormone of myosin light chain phosphorylation and aquaporin 5 protein expression in intact lung
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ORIGINAL PAPER
Modulation by thyroid hormone of myosin light chain phosphorylation and aquaporin 5 protein expression in intact lung Naser Pajouhi & Mohammad Owji & Fakhraddin Naghibalhossaini & Gholam H. R. Omrani & Masoumeh Varedi
Received: 5 November 2014 / Accepted: 21 January 2015 / Published online: 4 February 2015 # University of Navarra 2015
Abstract Myosin light chain kinase (MLCK) may play a key role in cellular contraction, paracellular permeability and lung water homeostasis. In vitro, thyroid hormones (THs) potently inhibit MLCK activation and, hence, MLC phosphorylation. Whether similar effect is exerted by THs in in vivo systems is not known. Therefore, we investigated the effects of hypothyroid (HO) and hyperthyroid (HR) states on the level of phospho-MLC, aquaporin 5 (AQP5) protein expression, and water holding capacity in the rat lung. Alterations in thyroid state were induced by adding methimazole or levothyroxine (L-T4) to animals’ drinking water. Serum TH concentration and thyroid gland histomorphology were assessed to verify the onset of the thyroid state. Lung phospho-MLC and AQP5 proteins were assessed
by Western blotting and immunohistochemistry. Lung extravascular water content was estimated by the tissue wet weight-to-dry weight (W/D) ratio. The HO state induced significant increases in the expression of lung phospho-MLC and AQP5 proteins. In contrast, the HR state caused moderate decreases in lung phospho-MLC and AQP5 proteins. While lung water holding capacity was significantly increased in HO animals, it was significantly reduced in HR animals. The data of this study show that THs are able to modulate MLC phosphorylation in in vivo systems. Besides, they suggest that the circulating level of THs may alter lung fluid balance not only through expression of water channels but also through regulation of cellular contraction and paracellular permeability.
N. Pajouhi : M. Varedi (*) Department of Physiology, School of Medicine, Shiraz University of Medical Sciences, Shiraz 7134853185, Iran e-mail: [email protected]
Keywords Thyroid . Myosin light chain . Phosphorylation . Aquaporin 5 . Epithelial/endothelial barrier
M. Owji Department of Pathology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
Introduction
F. Naghibalhossaini Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran G. H. R. Omrani Endocrine and Metabolism Research Center, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
Thyroid hormones (THs) play roles in the physiology of fetal, neonatal, and adult organs [32]. Permissive roles of THs in respect of promotion in the development and maturation of endothelial/epithelial barriers are well known [16]. However, little is known about their roles in the barrier functions in health and diseases. Accumulating data from several lines of studies have proven that severe trauma/stress such as cardiac surgery
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and ventilator-induced lung injury (VILI) are associated with marked redu
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