Vacuolar ATPase regulates surfactant secretion in rat alveolar type II cells by modulating lamellar body calcium. 2010

Narendranath Reddy Chintagari, and Amarjit Mishra, and Lijing Su, and Yang Wang, and Sahlu Ayalew, and Steven D Hartson, and Lin Liu
Lundberg-Kienlen Lung Biology and Toxicology Laboratory, Department of Physiological Sciences, Oklahoma State University, Stillwater, Oklahoma, United States of America.

Lung surfactant reduces surface tension and maintains the stability of alveoli. How surfactant is released from alveolar epithelial type II cells is not fully understood. Vacuolar ATPase (V-ATPase) is the enzyme responsible for pumping H(+) into lamellar bodies and is required for the processing of surfactant proteins and the packaging of surfactant lipids. However, its role in lung surfactant secretion is unknown. Proteomic analysis revealed that vacuolar ATPase (V-ATPase) dominated the alveolar type II cell lipid raft proteome. Western blotting confirmed the association of V-ATPase a1 and B1/2 subunits with lipid rafts and their enrichment in lamellar bodies. The dissipation of lamellar body pH gradient by Bafilomycin A1 (Baf A1), an inhibitor of V-ATPase, increased surfactant secretion. Baf A1-stimulated secretion was blocked by the intracellular Ca(2+) chelator, BAPTA-AM, the protein kinase C (PKC) inhibitor, staurosporine, and the Ca(2+)/calmodulin-dependent protein kinase II (CaMKII), KN-62. Baf A1 induced Ca(2+) release from isolated lamellar bodies. Thapsigargin reduced the Baf A1-induced secretion, indicating cross-talk between lamellar body and endoplasmic reticulum Ca(2+) pools. Stimulation of type II cells with surfactant secretagogues dissipated the pH gradient across lamellar bodies and disassembled the V-ATPase complex, indicating the physiological relevance of the V-ATPase-mediated surfactant secretion. Finally, silencing of V-ATPase a1 and B2 subunits decreased stimulated surfactant secretion, indicating that these subunits were crucial for surfactant secretion. We conclude that V-ATPase regulates surfactant secretion via an increased Ca(2+) mobilization from lamellar bodies and endoplasmic reticulum, and the activation of PKC and CaMKII. Our finding revealed a previously unrealized role of V-ATPase in surfactant secretion.

UI MeSH Term Description Entries
D008297 Male Males
D011493 Protein Kinase C An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters. Calcium Phospholipid-Dependent Protein Kinase,Calcium-Activated Phospholipid-Dependent Kinase,PKC Serine-Threonine Kinase,Phospholipid-Sensitive Calcium-Dependent Protein Kinase,Protein Kinase M,Calcium Activated Phospholipid Dependent Kinase,Calcium Phospholipid Dependent Protein Kinase,PKC Serine Threonine Kinase,Phospholipid Sensitive Calcium Dependent Protein Kinase,Phospholipid-Dependent Kinase, Calcium-Activated,Serine-Threonine Kinase, PKC
D011650 Pulmonary Alveoli Small polyhedral outpouchings along the walls of the alveolar sacs, alveolar ducts and terminal bronchioles through the walls of which gas exchange between alveolar air and pulmonary capillary blood takes place. Alveoli, Pulmonary,Alveolus, Pulmonary,Pulmonary Alveolus
D011663 Pulmonary Surfactants Substances and drugs that lower the SURFACE TENSION of the mucoid layer lining the PULMONARY ALVEOLI. Surfactants, Pulmonary,Pulmonary Surfactant,Surfactant, Pulmonary
D002118 Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D004791 Enzyme Inhibitors Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D006863 Hydrogen-Ion Concentration The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH pH,Concentration, Hydrogen-Ion,Concentrations, Hydrogen-Ion,Hydrogen Ion Concentration,Hydrogen-Ion Concentrations
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D015153 Blotting, Western Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes. Immunoblotting, Western,Western Blotting,Western Immunoblotting,Blot, Western,Immunoblot, Western,Western Blot,Western Immunoblot,Blots, Western,Blottings, Western,Immunoblots, Western,Immunoblottings, Western,Western Blots,Western Blottings,Western Immunoblots,Western Immunoblottings
D015180 Electrophoresis, Gel, Two-Dimensional Electrophoresis in which a second perpendicular electrophoretic transport is performed on the separate components resulting from the first electrophoresis. This technique is usually performed on polyacrylamide gels. Gel Electrophoresis, Two-Dimensional,Polyacrylamide Gel Electrophoresis, Two-Dimensional,2-D Gel Electrophoresis,2-D Polyacrylamide Gel Electrophoresis,2D Gel Electrophoresis,2D PAGE,2D Polyacrylamide Gel Electrophoresis,Electrophoresis, Gel, 2-D,Electrophoresis, Gel, 2D,Electrophoresis, Gel, Two Dimensional,Polyacrylamide Gel Electrophoresis, 2-D,Polyacrylamide Gel Electrophoresis, 2D,Two Dimensional Gel Electrophoresis,2 D Gel Electrophoresis,2 D Polyacrylamide Gel Electrophoresis,Electrophoresis, 2-D Gel,Electrophoresis, 2D Gel,Electrophoresis, Two-Dimensional Gel,Gel Electrophoresis, 2-D,Gel Electrophoresis, 2D,Gel Electrophoresis, Two Dimensional,PAGE, 2D,Polyacrylamide Gel Electrophoresis, 2 D,Polyacrylamide Gel Electrophoresis, Two Dimensional,Two-Dimensional Gel Electrophoresis

Related Publications

Narendranath Reddy Chintagari, and Amarjit Mishra, and Lijing Su, and Yang Wang, and Sahlu Ayalew, and Steven D Hartson, and Lin Liu
July 1991, American journal of respiratory cell and molecular biology,
Narendranath Reddy Chintagari, and Amarjit Mishra, and Lijing Su, and Yang Wang, and Sahlu Ayalew, and Steven D Hartson, and Lin Liu
June 1986, Biochimica et biophysica acta,
Narendranath Reddy Chintagari, and Amarjit Mishra, and Lijing Su, and Yang Wang, and Sahlu Ayalew, and Steven D Hartson, and Lin Liu
November 2023, Cellular & molecular biology letters,
Narendranath Reddy Chintagari, and Amarjit Mishra, and Lijing Su, and Yang Wang, and Sahlu Ayalew, and Steven D Hartson, and Lin Liu
January 2022, Science China. Life sciences,
Narendranath Reddy Chintagari, and Amarjit Mishra, and Lijing Su, and Yang Wang, and Sahlu Ayalew, and Steven D Hartson, and Lin Liu
February 2009, Cell and tissue research,
Narendranath Reddy Chintagari, and Amarjit Mishra, and Lijing Su, and Yang Wang, and Sahlu Ayalew, and Steven D Hartson, and Lin Liu
March 1996, Pediatric research,
Narendranath Reddy Chintagari, and Amarjit Mishra, and Lijing Su, and Yang Wang, and Sahlu Ayalew, and Steven D Hartson, and Lin Liu
May 1988, Biochimica et biophysica acta,
Narendranath Reddy Chintagari, and Amarjit Mishra, and Lijing Su, and Yang Wang, and Sahlu Ayalew, and Steven D Hartson, and Lin Liu
March 1988, The Journal of biological chemistry,
Narendranath Reddy Chintagari, and Amarjit Mishra, and Lijing Su, and Yang Wang, and Sahlu Ayalew, and Steven D Hartson, and Lin Liu
May 2008, American journal of respiratory cell and molecular biology,
Narendranath Reddy Chintagari, and Amarjit Mishra, and Lijing Su, and Yang Wang, and Sahlu Ayalew, and Steven D Hartson, and Lin Liu
August 2007, American journal of physiology. Lung cellular and molecular physiology,
Copied contents to your clipboard!