Genetic mechanisms for adrenergic control during stress

Annals of the New York Academy of Sciences
Dona Lee WongR Kvetnansky

Abstract

Cortisol and epinephrine released in response to stress are replenished via activation of the hypothalamic-pituitary-adrenal (HPA or stress) axis. Immobilization (IMMO) stress in rats stimulates epinephrine production in part via the gene encoding the epinephrine-synthesizing enzyme phenylethanolamine N-methyltransferase (PNMT). PNMT mRNA rose up to 7.0-fold with acute or chronic stress. Two transcription factors mediating stress induction of the PNMT gene are the glucocorticoid receptor (GR) and Egr-1, which interact with -533, -759, and -773 bp, and -165 bp binding sites in the rat PNMT promoter, respectively. To identify molecular mechanisms involved, effects of hypoxic stress on PNMT promoter activity were examined in PC12 cells transfected with the PNMT promoter-luciferase reporter gene construct pGL3RP893. Oxygen reduction to 5% increased PNMT promoter-driven luciferase expression, with maximum activity at 6 h. Pretreatment of the cells with protein kinase A (PKA) and protein kinase C (PKC) inhibitors, H-89 and GF109203X, respectively, attenuated the rise in luciferase. Similarly, PKA-deficient PC12 cells transfected with pGL3RP893 and exposed to hypoxia also showed attenuated PNMT promoter-driven luciferase expression. M...Continue Reading

References

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Nov 20, 2002·Annals of the New York Academy of Sciences·Dona Lee WongTze-Chun Tai
Nov 20, 2002·Annals of the New York Academy of Sciences·Michael G ZieglerRobert Enns

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Citations

Apr 29, 2006·Cellular and Molecular Neurobiology·Dona Lee Wong
Apr 21, 2009·Genome Biology·Atsutaka KubosakiYoshihide Hayashizaki
Oct 19, 2011·Oxidative Medicine and Cellular Longevity·James A G CrispoT C Tai
Apr 30, 2008·Human Mutation·Jan HaavikBeat Thöny
Jan 6, 2009·Annals of the New York Academy of Sciences·Richard KvetnanskýLucia Kubovcakova
Jan 6, 2009·Annals of the New York Academy of Sciences·Xiaoping LiuEsther L Sabban
Jun 28, 2013·Basic & Clinical Pharmacology & Toxicology·Stefanie KlenkeUlrich Hermann Frey
Aug 19, 2007·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Charles A DucsayDean A Myers
Jul 16, 2015·American Journal of Physiology. Endocrinology and Metabolism·Elizabeth A NewbyCharles A Ducsay
Apr 4, 2009·Physiological Reviews·Richard KvetnanskyMiklos Palkovits

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