RRC ID 12210
Author Hamada K, Takuwa N, Yokoyama K, Takuwa Y.
Title Stretch activates Jun N-terminal kinase/stress-activated protein kinase in vascular smooth muscle cells through mechanisms involving autocrine ATP stimulation of purinoceptors.
Journal J Biol Chem
Abstract Mechanical strain has been implicated in phenotypic changes, including alteration of gene expression in vascular smooth muscle cells; however, the molecular basis for mechanotransduction leading to nuclear gene expression is largely unknown. We demonstrate in the present study that cyclic stretching of vascular smooth muscle cells dramatically activates Jun N-terminal kinase (JNK)/stress-activated protein kinase (SAPK) through an autocrine mechanism. Stretch causes time- and strength-dependent rise of the ATP concentration in media. The stretch-induced activation JNK/SAPK is attenuated by the addition of hexokinase or apyrase that scavenge ATP in media. Both the P2 receptor antagonist and the A1 subtype-selective P1 receptor antagonist partially inhibit stretch-induced activation of JNK/SAPK. The conditioned medium from stretched cells contains an activity to stimulate JNK/SAPK. The JNK-stimulating activity in the conditioned medium from stretched cells is attenuated by the addition of apyrase or P1 and P2 receptor antagonists. The addition of exogenous ATP or adenosine induces dose-dependent activation of JNK/SAPK. These results indicate that stretch activates JNK/SAPK in vascular smooth muscle cells through mechanisms involving autocrine stimulation of purinoceptors by ATP and its hydrolyzed product adenosine.
Volume 273(11)
Pages 6334-40
Published 1998-3-13
DOI 10.1074/jbc.273.11.6334
PMID 9497362
MeSH Adenosine Triphosphate / metabolism* Angiotensin II / pharmacology Animals Aorta / cytology Autocrine Communication Calcium-Calmodulin-Dependent Protein Kinases / metabolism* Culture Media, Conditioned Enzyme Activation Gene Expression Regulation Genes, Immediate-Early JNK Mitogen-Activated Protein Kinases Mitogen-Activated Protein Kinases* Muscle, Smooth, Vascular / physiology* Parathyroid Hormone / biosynthesis* Parathyroid Hormone-Related Protein Peptide Fragments / biosynthesis* Physical Stimulation Proteins* Purinergic Antagonists Rats Rats, Wistar Receptors, Purinergic / metabolism* Signal Transduction
IF 4.238
Times Cited 100
DNA material pBS rcjun-1 (RDB01130) c-jun -730 -79 CAT (RDB01362)