The NAD+ precursor nicotinamide governs neuronal survival during oxidative stress through protein kinase B coupled to FOXO3a and mitochondrial membrane potential

Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism
Zhao Zhong ChongKenneth Maiese

Abstract

Nicotinamide, a beta-nicotinamide adenine dinucleotide (NAD) precursor and an essential nutrient for cell growth and function, may offer critical insights into the specific cellular mechanisms that determine neuronal survival, since this agent significantly impacts upon both neuronal and vascular integrity in the central nervous system. The authors show that nicotinamide provides broad, but concentration-specific, protection against apoptotic genomic DNA fragmentation and membrane phosphatidylserine exposure during oxidative stress to secure cellular integrity and prevent phagocytic cellular demise. Activation of the protein kinase B (Akt1) pathway is a necessary requirement for nicotinamide protection, because transfection of primary hippocampal neurons with a plasmid encoding a kinase-deficient dominant-negative Akt1 as well as pharmacologic inhibition of phosphatidylinositol-3-kinase phosphorylation of Akt1 eliminates cytoprotection by nicotinamide. Nicotinamide fosters neuronal survival through a series of intimately associated pathways. At one level, nicotinamide directly modulates mitochondrial membrane potential and pore formation to prevent cytochrome c release and caspase-3-and 9-like activities through mechanisms that...Continue Reading

References

Feb 2, 1999·Experimental Cell Research·A M Vincent, K Maiese
Jun 8, 1999·The Journal of Biological Chemistry·G RenaP Cohen
Sep 20, 2000·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·S H LinK Maiese
Oct 31, 2000·The Journal of Biological Chemistry·A YamaguchiM Tohyama
May 11, 2002·Journal of Cellular and Molecular Medicine·Robert JesselHorst A Diehl
Sep 7, 2002·Antioxidants & Redox Signaling·Shugo UedaJunji Yodoi
Feb 8, 2003·Archives of Biochemistry and Biophysics·Gianluigi La PianaNicola E Lofrumento
Mar 7, 2003·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Zhao Zhong ChongKenneth Maiese
Mar 11, 2003·The Journal of Pharmacy and Pharmacology·Kozo YaoTetsuji Ohno
May 28, 2003·Trends in Pharmacological Sciences·Kenneth Maiese, Zhao Zhong Chong
Jul 30, 2003·Archives of Internal Medicine·Nicole Simpkins, Joseph Jankovic

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Citations

Jan 6, 2005·JAMA : the Journal of the American Medical Association·Kenneth MaieseZhao Zhong Chong
Dec 14, 2011·Journal of Molecular Neuroscience : MN·Najeeb UllahMyeong Ok Kim
Jun 19, 2007·Antioxidants & Redox Signaling·Masahiro OkouchiTak Yee Aw
Sep 6, 2011·The Journal of Veterinary Medical Science·Jin-Hee SungPhil-Ok Koh
Oct 31, 2012·International Journal of Molecular Sciences·Kenneth MaieseShaohui Wang
Dec 4, 2012·International Journal of Molecular Sciences·Kenneth MaieseYan Chen Shang
Sep 29, 2009·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Kenneth MaieseYan Chen Shang
Jul 1, 2008·Oxidative Medicine and Cellular Longevity·Kenneth MaieseJinling Hou
Jul 2, 2010·Oxidative Medicine and Cellular Longevity·Kenneth MaieseYan Chen Shang
Aug 19, 2010·Oxidative Medicine and Cellular Longevity·Kenneth MaieseYan Chen Shang
Jun 17, 2008·Expert Opinion on Therapeutic Targets·Kenneth MaieseJinling Hou
Oct 25, 2012·Expert Opinion on Drug Discovery·Kenneth MaieseShaohui Wang
Sep 18, 2012·Progress in Neurobiology·Zhao Zhong ChongKenneth Maiese
Jun 18, 2010·Neurobiology of Disease·Amjad ShehadahMichael Chopp
May 8, 2010·European Journal of Pharmacology·Robert NowakJolanta Tarasiuk
Mar 24, 2010·Mechanisms of Ageing and Development·Ping Xu, Anthony A Sauve
Nov 26, 2015·The International Journal of Biochemistry & Cell Biology·Jing WuFengmin Zhang
Apr 9, 2008·Progress in Neurobiology·Kenneth MaieseYan Chen Shang
Apr 12, 2008·Trends in Molecular Medicine·Kenneth MaieseYan Chen Shang
Feb 27, 2008·Cytokine & Growth Factor Reviews·Kenneth MaieseYan Chen Shang
Mar 18, 2008·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Kenneth Maiese
Mar 4, 2008·Pharmacology & Therapeutics·Kenneth MaieseYan Chen Shang
Nov 6, 2008·Medicinal Research Reviews·Kenneth MaieseJinling Hou
Oct 18, 2006·The European Journal of Neuroscience·Ai-Li CaiChristian T Sheline
Aug 21, 2010·The European Journal of Neuroscience·Christian T ShelineChunxiao Shi
Mar 12, 2010·Journal of Clinical Pharmacology·Kenneth MaieseJinling Hou
Jun 18, 2005·Brain Research. Brain Research Reviews·Zhao Zhong ChongKenneth Maiese
Jul 24, 2015·Molecular Nutrition & Food Research·Ching-Hsia HungKun-Ling Tsai
Jan 31, 2006·Archives of Gerontology and Geriatrics·Jaime MiquelJoaquin Diaz Alperi
Mar 15, 2006·Brain Research Bulletin·Yangzheng FengMichael H LeBlanc
Jan 31, 2008·Biochemical and Biophysical Research Communications·Hyung Il LeeEun Seong Hwang

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Methods Mentioned

BETA
transfection
electrophoresis

Software Mentioned

NIH Image

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