| 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
|
| PII |
S0021-9258(18)67750-6
|
| 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
|
|
WOS Category
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| Resource |
| DNA material |
pBS rcjun-1 (RDB01130) c-jun -730
-79 CAT (RDB01362) |
