Resveratrol stimulates cortisol biosynthesis by activating SIRT-dependent deacetylation of P450scc.

Endocrinology
Donghui LiMarion B Sewer

Abstract

In the human adrenal cortex, cortisol is synthesized from cholesterol by members of the cytochrome P450 superfamily and hydroxysteroid dehydrogenases. Both the first and last steps of cortisol biosynthesis occur in mitochondria. Based on our previous findings that activation of ACTH signaling changes the ratio of nicotinamide adenine dinucleotide (NAD) phosphate to reduced NAD phosphate in adrenocortical cells, we hypothesized that pyridine nucleotide metabolism may regulate the activity of the mitochondrial NAD(+)-dependent sirtuin (SIRT) deacetylases. We show that resveratrol increases the protein expression and half-life of P450 side chain cleavage enzyme (P450scc). The effects of resveratrol on P450scc protein levels and acetylation status are dependent on SIRT3 and SIRT5 expression. Stable overexpression of SIRT3 abrogates the cellular content of acetylated P450scc, concomitant with an increase in P450scc protein expression and cortisol secretion. Mutation of K148 and K149 to alanine stabilizes the expression of P450scc and results in a 1.5-fold increase in pregnenolone biosynthesis. Finally, resveratrol also increases the protein expression of P450 11β, another mitochondrial enzyme required for cortisol biosynthesis. Coll...Continue Reading

References

Apr 1, 1994·Molecular and Cellular Endocrinology·W E RaineyJ I Mason
Jun 1, 1993·DNA and Cell Biology·J A HarikrishnaW L Miller
Jun 30, 2001·Molecular Cell·Q Ren, M A Gorovsky
Jun 26, 2003·DNA and Cell Biology·Pavel A NazarovLyudmila A Novikova
Aug 27, 2003·Nature·Konrad T HowitzDavid A Sinclair
Jan 27, 2004·Journal of Leukocyte Biology·Stephen W BuckJeffrey S Smith
May 6, 2004·The Journal of Biological Chemistry·Armando van der HorstBoudewijn M T Burgering
Jun 4, 2004·Nature·Frédéric PicardLeonard Guarente
Jul 20, 2004·The Journal of Biological Chemistry·Jason K YanoEric F Johnson
Aug 17, 2004·Trends in Cell Biology·Maria E Giannakou, Linda Partridge
Feb 5, 2005·The EMBO Journal·Yonghua YangWenlong Bai
Aug 5, 2005·Molecular Biology of the Cell·Eriko MichishitaIzumi Horikawa
Aug 27, 2005·Current Opinion in Chemical Biology·John M Denu
Nov 18, 2005·Gene·Michele A GlozakEdward Seto
Apr 14, 2006·Current Drug Targets·Dominique DelmasNorbert Latruffe
May 11, 2006·Trends in Endocrinology and Metabolism : TEM·Tianle YangAnthony A Sauve
May 24, 2006·The Journal of Cell Biology·Chad D KnightsMaria Laura Avantaggiati
Jun 22, 2006·Proceedings of the National Academy of Sciences of the United States of America·Bjoern SchwerEric Verdin
Jun 23, 2006·Proceedings of the National Academy of Sciences of the United States of America·William C HallowsJohn M Denu
Jul 4, 2006·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Carl-Magnus BäckesjöLars-Arne Haldosén
Aug 23, 2006·Molecular and Cellular Biology·Maofu FuRichard G Pestell
Sep 5, 2006·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·H Faus, B Haendler
Dec 21, 2006·Clinical and Experimental Immunology·S SharmaJ N Agrewala
Feb 20, 2007·Toxicology and Applied Pharmacology·Mohammad AtharArianna L Kim
Apr 5, 2007·Journal of Biochemistry·Takashi Ito
Apr 24, 2007·The Biochemical Journal·Shaday Michan, David Sinclair
Apr 26, 2007·Cell Cycle·Toshiaki InoueMitsuo Oshimura
Aug 8, 2007·Biochimie·Karin SadoulSaadi Khochbin
Aug 19, 2007·Annals of Medicine·Nassim Dali-YoucefJohan Auwerx
Oct 10, 2007·Molecular and Cellular Biology·David B LombardBjoern Schwer

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Citations

Jan 30, 2016·Trends in Biochemical Sciences·Josue BaezaJohn M Denu
Oct 30, 2012·Free Radical Biology & Medicine·Brian J Morris
May 23, 2013·American Journal of Physiology. Endocrinology and Metabolism·Natasa J StojkovSilvana A Andric
Nov 9, 2018·Frontiers in Endocrinology·Masaaki Yamamoto, Yutaka Takahashi
Jun 11, 2019·Oxidative Medicine and Cellular Longevity·Xiaolu QuZhendan Shi

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