Melatonin attenuates isoproterenol-induced protein kinase A overactivation and tau hyperphosphorylation in rat brain

Journal of Pineal Research
Dan Ling WangJian-Zhi Wang

Abstract

Hyperphosphorylation of microtubule-associated protein tau at specific sites is a recognized pathological process in Alzheimer's disease (AD), and protein kinase A (PKA) is a crucial kinase in AD-like tau hyperphosphorylation. In the present study, isoproterenol (ISO) was injected bilaterally into hippocampus of rat brain; ISO is a specific PKA activator and it induces tau hyperphosphorylation. With this system, melatonin (MT) was shown to protect against ISO-induced tau hyperphosphorylation. We found that hippocampal injection of ISO (0.02 microm) induced PKA overactivation and tau hyperphosphorylation at both paired helical filament (PHF)-1 and tau-1 sites. ISO injection also resulted in activation of superoxide dismutase (SOD) and elevation of malondialdehyde (MDA), parameters suggesting elevated oxidative stress. Preinfusion of MT intraperitoneally partially reversed ISO-induced tau hyperphosphorylation at the PHF-1 epitope (1 and 10 mg/kg continuously for 4 wk or 10 mg/kg for 1, 2 or 3 wk) and tau-1 epitope (10 mg/kg for 2 wk). Furthermore, MT (10 mg/kg for 2 wk) obviously antagonized ISO-induced PKA overactivation, as well as enhanced SOD activity and decreased the level of MDA. It is suggested from these data that ISO ma...Continue Reading

Citations

Mar 3, 2005·European Journal of Pharmacology·Xia-Chun LiJian-Zhi Wang
Dec 21, 2005·Acta Pharmacologica Sinica·Jian-zhi Wang, Ze-fen Wang
Jan 18, 2006·Acta Pharmacologica Sinica·Yong ChengJun-tian Zhang
May 11, 2010·Drugs & Aging·Cheng-Xin GongKhalid Iqbal
Jul 17, 2013·International Journal of Molecular Sciences·Li LinQing Tian
Aug 14, 2012·Oxidative Medicine and Cellular Longevity·Ye Feng, Xiaochuan Wang
Apr 22, 2005·Acta Pharmacologica Sinica·Yan-qiu DengJian-zhi Wang
Mar 23, 2007·FEBS Letters·Qing-Guo RenJian-Zhi Wang
Sep 2, 2006·The Journal of Pharmacy and Pharmacology·Germaine EscamesRussel J Reiter
Jan 20, 2011·Journal of Pineal Research·Yu-Fang XiongHong-Xing Wang
Oct 13, 2009·CNS Neuroscience & Therapeutics·Xin Wang
Jun 13, 2006·IEEE Engineering in Medicine and Biology Magazine : the Quarterly Magazine of the Engineering in Medicine & Biology Society·Elizabeth M FloodHarold R Garner
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