Inhibition of endogenous TRP1 decreases capacitative Ca2+entry and attenuates pulmonary artery smooth muscle cell proliferation
| Autor: | Shen Zhang, Jason X.-J. Yuan, Ying Yu, Oleksandr Platoshyn, Michele Sweeney, Sharon S. McDaniel |
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| Rok vydání: | 2002 |
| Předmět: |
Pulmonary and Respiratory Medicine
medicine.medical_specialty Cell division Physiology Gene Expression chemistry.chemical_element Endogeny Pulmonary Artery Biology Calcium Muscle Smooth Vascular Membrane Potentials Transient receptor potential channel Nickel Physiology (medical) Internal medicine medicine.artery medicine Humans RNA Messenger Growth Substances Cells Cultured TRPC Cation Channels Membrane potential Voltage-dependent calcium channel Cell growth Blood Proteins Cell Biology Oligonucleotides Antisense Endocrinology chemistry Pulmonary artery Calcium Channels Ion Channel Gating Cell Division |
| Zdroj: | American Journal of Physiology-Lung Cellular and Molecular Physiology. 283:L144-L155 |
| ISSN: | 1522-1504 1040-0605 |
| DOI: | 10.1152/ajplung.00412.2001 |
| Popis: | Pulmonary vascular medial hypertrophy due to proliferation of pulmonary artery smooth muscle cells (PASMC) greatly contributes to the increased pulmonary vascular resistance in pulmonary hypertension patients. A rise in cytosolic free Ca2+concentration ([Ca2+]cyt) is an important stimulus for cell growth in PASMC. Resting [Ca2+]cyt, intracellularly stored [Ca2+], capacitative Ca2+entry (CCE), and store-operated Ca2+currents ( ISOC) are greater in proliferating human PASMC than in growth-arrested cells. Expression of TRP1, a transient receptor potential gene proposed to encode the channels responsible for CCE and ISOC, was also upregulated in proliferating PASMC. Our aim was to determine if inhibition of endogenous TRP1 gene expression affects ISOCand CCE and regulates cell proliferation in human PASMC. Cells were treated with an antisense oligonucleotide (AS, for 24 h) specifically designed to cleave TRP1 mRNA and then returned to normal growth medium for 40 h before the experiments. Then, mRNA and protein expression of TRP1 was downregulated, and amplitudes of ISOCand CCE elicited by passive depletion of Ca2+from the sarcoplasmic reticulum using cyclopiazonic acid were significantly reduced in the AS-treated PASMC compared with control. Furthermore, the rate of cell growth was decreased by 50% in AS-treated PASMC. These results indicate that TRP1 may encode a store-operated Ca2+channel that plays a critical role in PASMC proliferation by regulating CCE and intracellular [Ca2+]cyt. |
| Databáze: | OpenAIRE |
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