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Nitric oxide regulates prolidase activity by serine/threonine phosphorylation
Arkadiusz Surazynski1, Yongmin Liu, Wojciech Miltyk
1Metabolism and Cancer Susceptibility Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute at Frederick, Frederick, Maryland 21702, USA.
Journal of Cellular Biochemistry
|September 17, 2005
Summary
Nitric oxide (NO) enhances prolidase activity by increasing its phosphorylation through the PKG-cGMP pathway, independent of MAPK signaling. This reveals a novel link between NO signaling and matrix degradation regulation.
Area of Science:
- Biochemistry
- Cell Biology
- Molecular Signaling
Background:
- Prolidase is a key enzyme in collagen metabolism and matrix remodeling.
- Nitric oxide (NO) is a signaling molecule involved in processes like collagen synthesis and angiogenesis.
- The interaction between NO and prolidase activity was previously unexplored.
Purpose of the Study:
- To investigate the regulatory effect of nitric oxide (NO) on prolidase activity.
- To elucidate the molecular mechanisms underlying NO-mediated prolidase activation.
- To determine the signaling pathways involved in NO-dependent prolidase modulation.
Main Methods:
- Utilized NO donors (SIN-1, DETA/NO) and inducible nitric oxide synthase (iNOS) expression to modulate NO levels.
- Assessed prolidase activity and expression in response to NO.
- Investigated protein phosphorylation, specifically serine/threonine phosphorylation on prolidase.
- Examined the roles of cGMP and MAPK pathways using agonists, inhibitors, and specific pathway inhibitors (e.g., Rp-8-Br-pCPT-cGMP, ERK1/2 inhibitor).
Main Results:
- Both exogenous and endogenous NO significantly increased prolidase activity in a time- and dose-dependent manner.
- Increased prolidase activity was not associated with altered prolidase expression.
- NO treatment led to increased serine/threonine phosphorylation of prolidase.
- Activation of the PKG-cGMP pathway mimicked NO's effect on prolidase activity and phosphorylation.
- Inhibition of cGMP signaling abolished NO-induced prolidase activation.
- The MAPK pathway (ERK1/2) was not involved in NO-dependent prolidase activation.
Conclusions:
- Nitric oxide stimulates prolidase activity via serine/threonine phosphorylation.
- The PKG-cGMP pathway mediates NO-dependent prolidase activation.
- MAPK signaling is not involved in this NO-mediated regulatory mechanism.
- This study highlights a novel interaction between NO signaling and the regulation of matrix degradation.