Gene Regulation of Catecholamine Biosynthetic Enzymes by Nitric Oxide in PC12 Cells

Dominique Ansell,Julie Grandbois,T C Tai

doi:10.4236/ojemd.2014.44009

Dominique Ansell, Julie Grandbois + Show 1 more

Open Access

https://doi.org/10.4236/ojemd.2014.44009

Copy DOI

Abstract

Nitric oxide (NO) regulates a wide range of physiological processes. Recent studies show that NO can regulate the release of catecholamines (CA) from the adrenal medulla. In the current study, the PC12 cell line was used to examine the effect of NO on the regulation of the CA biosynthetic enzymes: tyrosine hydroxylase (TH), dopamine-β-hydroxylase (DBH) and phenylethanolamine Nmethyltransferase (PNMT). Treatment of PC12 cells with the NO donor, sodium nitroprusside (SNP) for 6 hours significantly increased TH, DBH and PNMT mRNA levels. In addition, NO potentiates the regulation of gene expression of all three CA biosynthetic enzymes by glucocorticoids and cholinergic agonists. The signaling pathways involved in NO regulation of CA biosynthetic enzymes were investigated with the use of specific kinase activators and inhibitors, with results supporting a contributing role of PKA, PKC and PKG in SNP-mediated induction for all three CA genes (p

Highlights

Nitric oxide (NO) is a volatile gas that has been associated with a wide range of physiological processes
RT-PCR analysis from PC12 cells treated for 6 h with the NO donor (100 μM sodium nitroprusside (SNP)) significantly increased tyrosine hydroxylase (TH)
To determine the impact of NO elevations on cholinergic regulation of CA biosynthetic enzymes, RT-PCR analysis from PC12 cells treated for 6 h with specific cholinergic receptor agonists and SNP was conducted (Figure 2(a))

Summary

Introduction

Nitric oxide (NO) is a volatile gas that has been associated with a wide range of physiological processes. NO is synthesized from L-arginine and molecular oxygen by nitric oxide synthase (NOS) which exists in various isoforms including neuronal (nNOS), endothelial (eNOS) and inducible (iNOS) [2]. The complete L-arginine/NO/cGMP pathway exists in the adrenal medulla, a tissue that is critically important in the regulation, synthesis and release of catecholamines (CA) during stress response [3] [5]. Recent studies show that NO increases the synthesis of adrenal CAs via induction of tyrosine hydroxylase (TH), dopamine β-hydroxylase (DBH) and phenylethanolamine N-methyltransferase (PNMT) via the cGMP-dependent signaling pathway [1]. SNP-derived NO has been shown to increase TH activity and the levels of norepinephrine and epinephrine in the adrenal medulla of rats [7]

Methods

Results

Conclusion