کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1950483 1055644 2015 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
SERCA and PMCA pumps contribute to the deregulation of Ca2 + homeostasis in human CF epithelial cells
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
SERCA and PMCA pumps contribute to the deregulation of Ca2 + homeostasis in human CF epithelial cells
چکیده انگلیسی


• This study deciphers the deregulation of Ca2 + homeostasis in CF cells.
• ER Ca2 + concentration is increased in CF cells compared to CF cells.
• SERCA pump activity is abnormally increased and PMCA activity decreased in CF cells.
• CFTR interacts with SERCA2b and PMCA. These interactions regulate pump activities.
• Treatment VX-809 correct most of the calcium homeostasis deregulations.

Cystic Fibrosis (CF) disease is caused by mutations in the CFTR gene (CF transmembrane conductance regulator). F508 deletion is the most represented mutation, and F508del-CFTR is absent of plasma membrane and accumulates into the endoplasmic reticulum (ER) compartment. Using specific Ca2 + genetics cameleon probes, we showed in the human bronchial CF epithelial cell line CFBE that ER Ca2 + concentration was strongly increased compared to non-CF (16HBE) cells, and normalized by the F508del-CFTR corrector agent, VX-809. We also showed that ER F508del-CFTR retention increases SERCA (Sarcoplasmic/Reticulum Ca2 + ATPase) pump activity whereas PMCA (Plasma Membrane Ca2 + ATPase) activities were reduced in these CF cells compared to corrected CF cells (VX-809) and non-CF cells. We are showing for the first time CFTR/SERCA and CFTR/PMCA interactions that are modulated in CF cells and could explain part of Ca2 + homeostasis deregulation due to mislocalization of F508del-CFTR. Using ER or mitochondria genetics Ca2 + probes, we are showing that ER Ca2 + content, mitochondrial Ca2 + uptake, SERCA and PMCA pump, activities are strongly affected by the localization of F508del-CFTR protein.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research - Volume 1853, Issue 5, May 2015, Pages 892–903
نویسندگان
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