Abstract
Aim:
This study was to investigate the effect of dehydroevodiamine (DHED) on Alzheimer's disease (AD)-like tau hyperphosphorylation induced by calyculin A (CA), an inhibitor of protein phosphatase (PP)-2A and PP-1, and the involvement of PP-2A in metabolically competent rat brain slices.
Methods:
Rat brain slices were pre-incubated at 33°C in the presence (10, 100, and 200 μmol/L, respectively) or absence of DHED for 1 h. Then, CA 0.1 μmol/L was added and the slices were treated for another 2 h. Western blotting and/or immunohistochemistry were used to measure the phosphorylation level of tau and PP-2A.
Results:
CA treatment could remarkably increase the immunoreactivity of pS262 and decrease the staining of Tau-1, representing tau hyperphosphorylation at Ser262 (pS262) and Ser198/ 199/202 (Tau-1, as the antibody reacts with unphosphorylated tau, therefore, decreased staining represents increased phosphorylation). Pre-incubation of the brain slices with DHED could efficiently attenuate the CA-induced tau hyperphosphorylation at the above AD-related sites. Additionally, DHED also decreased the basal phosphorylation level of tau at Ser396, although CA failed to induce tau hyperphosphorylation at this site. Furthermore, CA treatment induced an increased level of Tyr307-phosphorylated PP-2A, which represents inactivation of the phosphatase, whereas DHED arrested the elevation of the inhibitory modification of PP-2A.
Conclusion:
DHED can attenuate CA-induced tau hyperphosphorylation at multiple AD-related sites in metabolically active rat brain slices. The underlying mechanism may involve a decreased inhibitory phosphorylation of PP-2A at Tyr307.
Similar content being viewed by others
Article PDF
References
Grundke-Iqbal I, Iqbal K, Quinlan M, Tung YC, Zaidi MS, Wisniewski HM . Microtubule-associated protein tau. A component of Alzheimer paired helical filaments. J Biol Chem 1986; 261: 6084–9.
Grundke-Iqbal I, Iqbal K, Tung YC, Quinlan M, Wisniewski HM, Binder LI . Abnormal phosphorylation of the microtubule-associated protein tau (tau) in Alzheimer cytoskeletal pathology. Proc Natl Acad Sci USA 1986; 83: 4913–7.
Lee VM, Balin BJ, Otvos L Jr, Trojanowski JQ . A68: a major subunit of paired helical filaments and derivatized forms of normal Tau. Science 1991; 251: 675–8.
Masters CL, Simms G, Weinman NA, Multhaup G, McDonald BL, Beyreuther K . Amyloid plaque core protein in Alzheimer disease and Down syndrome. Proc Natl Acad Sci USA 1985; 82: 4245–9.
Davies P, Maloney AJ . Selective loss of central cholinergic neurons in Alzheimer's disease. Lancet 1976; 2: 1403.
Giacobini E . From molecular structure to Alzheimer therapy. Jpn J Pharmacol 1997; 74: 225–41.
Yamada K, Toshitaka N . Therapeutic approaches to the treatment of Alzheimer's disease. Drugs Today (Barc) 2002; 38: 631–7.
Iqbal K, Grundke-Iqbal I . Inhibition of neurofibrillary degeneration: a promising approach to Alzheimer's disease and other tauopathies. Curr Drug Targets 2004; 5: 495–502.
Park CH, Kim SH, Choi W, Lee YJ, Kim JS, Kang SS, et al. Novel anticholinesterase and antiamnesic activities of dehydroevodiamine, a constituent of Evodia rutaecarpa. Planta Med 1996; 62: 405–9.
Park CH, Lee YJ, Lee SH, Choi SH, Kim HS, Jeong SJ, et al. Dehydroevodiamine·HCl prevents impairment of learning and memory and neuronal loss in rat models of cognitive disturbance. J Neurochem 2000; 74: 244–53.
Wang HH, Chou CJ, Liao JF, Chen CF . Dehydroevodiamine attenuates beta-amyloid peptide-induced amnesia in mice. Eur J Pharmacol 2001; 413: 221–5.
Arriagada PV, Growdon JH, Hedley-Whyte ET, Hugman BT . Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer's disease. Neurology 1992; 42: 631–9.
Riley KP, Snowdon DA, Markesbery WR . Alzheimer's neurofibrillary pathology and the spectrum of cognitive function: findings from the Nun Study. Ann Neurol 2002; 51: 567–77.
Wang JZ, Gong CX, Zaidi T, Grundke-Iqbal I, Iqbal K . Dephosphorylation of Alzheimer paired helical filaments by protein phosphatase-2A and -2B. J Biol Chem 1995; 270: 4854–60.
Wang JZ, Grundke-Iqbal I, Iqbal K . Restoration of biological activity of Alzheimer abnormally phosphorylated tau by dephosphorylation with protein phosphatase-2A, -2B and -1. Brain Res Mol Brain Res 1996; 38: 200–8.
Liu F, Grundke-Iqbal I, Iqbal K, Gong CX . Contributions of protein phosphatases PP1, PP2A, PP2B and PP5 to the regulation of tau phosphorylation. Eur J Neurosci 2005; 22: 1942–50.
Gong CX, Wegiel J, Zuck L, Grundke-Iqbal I, Iqbal K . Phosphorylation of microtubule-associated protein tau is regulated by protein phosphatase 2A in mammalian brain. Implications for neurofibrillary degeneration in Alzheimer's disease. J Biol Chem 2000; 275: 5535–44.
Gong CX, Shaikh S, Wang JZ, Zaidi T, Grundke-Iqbal I, Iqbal K . Phosphatase activity toward abnormally phosphorylated tau: decrease in Alzheimer disease brain. J Neurochem 1995; 65: 732–8.
Peng JH, Zhang CE, Wei W, Hong XP, Pan XP, Wang JZ . Dehydroevodiamine attenuates tau hyperphosphorylation and memory deficit induced by activation of glycogen synthase ki-nase-3 in rats. Neuropharmacology 2007; 52: 1521–7.
Chen J, Martin BL, Brautigan DL . Regulation of protein serine-threonine phosphatase type-2A by tyrosine phosphorylation. Science 1992; 257: 1261–4.
Gong CX, Liu F, Grundke-Iqbal I, Iqbal K . Dysregulation of protein phosphorylation/dephosphorylation in Alzheimer's disease: a therapeutic target. J Biomed Biotechnol 2006; 2006: 31825.
Braak H, Braak E . Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol (Berl) 1991, 82: 239–59.
Gong CX, Liu F, Grundke-Iqbal I, Iqbal K . Post-translational modifications of tau protein in Alzheimer's disease. J Neural Transm 2005; 112: 813–38.
Biernat J, Gustke N, Drewes G, Mandelkow EM, Mandelkow E . Phosphorylation of Ser262 strongly reduces binding of tau to microtubules: distinction between PHF-like immunoreactivity and microtubule binding. Neuron 1993; 11: 153–63.
Li XC, Wang ZF, Zhang JX, Wang Q, Wang JZ . Effect of melatonin on calyculin A-induced tau hyperphosphorylation. Eur J Pharmacol 2005; 510: 25–30.
Sontag E, Luangpirom A, Hladik C, Mudrak I, Ogris E, Speciale S, et al. Altered expression levels of the protein phosphatase 2A ABalphaC enzyme are associated with Alzheimer disease pathology. J Neuropathol Exp Neurol 2004; 63: 287–301.
Vogelsberg-Ragaglia V, Schuck T, Trojanowski JQ, Lee VM . PP2A mRNA expression is quantitatively decreased in Alzheimer's disease hippocampus. Exp Neurol 2001; 168: 402–12.
Tian Q, Lin ZQ, Wang XC, Chen J, Wang Q, Gong CX, et al. Injection of okadaic acid into the Meynert nucleus basalis of rat brain induces decreased acetylcholine level and spatial memory deficit. Neuroscience 2004; 126: 277–84.
Takada-Takatori Y, Kume T, Sugimoto M, Katsuki H, Sugimoto H, Akaike A . Acetylcholinesterase inhibitors used in treatment of Alzheimer's disease prevent glutamate neurotoxicity via nicoginic acetylcholine receptors and phosphatidylinositol 3-kinase cascade. Neuropharmacology 2006; 51: 474–86.
Ahn SH, Jeon SH, Tsuruo T, Shim CK, Chung SJ . Pharmacokinetic characterization of dehydroevodiamine in the rat brain. J Pharm Sci 2004; 93: 283–92.
Author information
Authors and Affiliations
Corresponding author
Additional information
This work was supported in part by grants from the Science and Technology Committee of China (No 2006AA02Z4A1 and 2006CB-500703), the Natural Science Foundation of China (No 30500188), and the Science and Technology Department of Hubei Province (No 2006ABC005).
Rights and permissions
About this article
Cite this article
Fang, J., Liu, R., Tian, Q. et al. Dehydroevodiamine attenuates calyculin A-induced tau hyperphos-phorylation in rat brain slices. Acta Pharmacol Sin 28, 1717–1723 (2007). https://doi.org/10.1111/j.1745-7254.2007.00655.x
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1111/j.1745-7254.2007.00655.x
Keywords
This article is cited by
-
Traditional Chinese medicine Euodiae Fructus: botany, traditional use, phytochemistry, pharmacology, toxicity and quality control
Natural Products and Bioprospecting (2023)
-
Anti-inflammatory and anti-infectious effects of Evodia rutaecarpa (Wuzhuyu) and its major bioactive components
Chinese Medicine (2011)