Hydrogen Peroxide Promotes Abeta Production Through JNK-dependent Activation of Gamma-secretase

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2008 Apr 26

PMID 18436531

Citations 79

Authors

Chengyong Shen

YongFeng Chen

Huaqing Liu

Kejing Zhang

Ting Zhang

Anning Lin

Naihe Jing

Affiliations

Soon will be listed here.

Abstract

Accumulation of senile plaques composed of amyloid beta-peptide (Abeta) is a pathological hallmark of Alzheimer disease (AD), and Abeta is generated through the sequential cleavage of amyloid precursor protein (APP) by beta- and gamma-secretase. Although oxidative stress has been implicated in the AD pathogenesis by inducing Abeta production, the underlying mechanism remains elusive. Here we show that the pro-oxidant H(2)O(2) promotes Abeta production through c-Jun N-terminal kinase (JNK)-dependent activation of gamma-secretase. Treatment with H(2)O(2) induced significant increase in the levels of intracellular and secreted Abeta in human neuroblastoma SH-SY5Y cells. Although gamma-secretase-mediated cleavage of APP or C99 was enhanced upon H(2)O(2) treatment, expression of APP or its alpha/beta-secretase-mediated cleavage was not affected. Silencing of the stress-activated JNK by small interfering RNA or the specific JNK inhibitor SP600125 reduced H(2)O(2)-induced gamma-secretase-mediated cleavage of APP. JNK activity was augmented in human brain tissues from AD patients and active JNK located surrounding the senile plaques in the brain of AD model mouse. Our data suggest that oxidative stress-activated JNK may contribute to senile plaque expansion through the promotion of gamma-secretase-mediated APP cleavage and Abeta production.

Citing Articles

A systematic review for the development of Alzheimer's disease in models: a focus on different inducing agents.

Prajapat M, Kaur G, Choudhary G, Pahwa P, Bansal S, Joshi R Front Aging Neurosci. 2024; 15:1296919.

PMID: 38173557 PMC: 10761490. DOI: 10.3389/fnagi.2023.1296919.

Multifunctional effect of flavonoids from against Alzheimer's disease pathogenesis.

Arsito P, Waiwut P, Yenjai C, Arthan S, Monthakantirat O, Nualkaew N Heliyon. 2023; 9(11):e21894.

PMID: 38106662 PMC: 10722324. DOI: 10.1016/j.heliyon.2023.e21894.

C9orf72 poly-GA proteins impair neuromuscular transmission.

Tu W, Xu W, Zhang J, Qi S, Bai L, Shen C Zool Res. 2023; 44(2):331-340.

PMID: 36799225 PMC: 10083233. DOI: 10.24272/j.issn.2095-8137.2022.356.

The cellular model for Alzheimer's disease research: PC12 cells.

Xie D, Deng T, Zhai Z, Sun T, Xu Y Front Mol Neurosci. 2023; 15:1016559.

PMID: 36683856 PMC: 9846650. DOI: 10.3389/fnmol.2022.1016559.

Pharmaceutical Potential of Casein-Derived Tripeptide Met-Lys-Pro: Improvement in Cognitive Impairments and Suppression of Inflammation in APP/PS1 Mice.

Matsuzaki Tada A, Hamezah H, Arrozi A, Bakar Z, Yanagisawa D, Tooyama I J Alzheimers Dis. 2022; 89(3):835-848.

PMID: 35964178 PMC: 9535549. DOI: 10.3233/JAD-220192.

References

Selkoe D, Wolfe M . Presenilin: running with scissors in the membrane. Cell. 2007; 131(2):215-21. DOI: 10.1016/j.cell.2007.10.012. View

Liao Y, Wang B, Cheng H, Kuo L, Wolfe M . Tumor necrosis factor-alpha, interleukin-1beta, and interferon-gamma stimulate gamma-secretase-mediated cleavage of amyloid precursor protein through a JNK-dependent MAPK pathway. J Biol Chem. 2004; 279(47):49523-32. DOI: 10.1074/jbc.M402034200. View

Selkoe D . Alzheimer's disease is a synaptic failure. Science. 2002; 298(5594):789-91. DOI: 10.1126/science.1074069. View

Funato H, Yoshimura M, KUSUI K, Tamaoka A, Ishikawa K, Ohkoshi N . Quantitation of amyloid beta-protein (A beta) in the cortex during aging and in Alzheimer's disease. Am J Pathol. 1998; 152(6):1633-40. PMC: 1858449. View

Finkel T, Holbrook N . Oxidants, oxidative stress and the biology of ageing. Nature. 2000; 408(6809):239-47. DOI: 10.1038/35041687. View

Benzing W, Wujek J, Ward E, Shaffer D, Ashe K, Younkin S . Evidence for glial-mediated inflammation in aged APP(SW) transgenic mice. Neurobiol Aging. 2000; 20(6):581-9. DOI: 10.1016/s0197-4580(99)00065-2. View

Zhu X, Raina A, Perry G, Smith M . Alzheimer's disease: the two-hit hypothesis. Lancet Neurol. 2004; 3(4):219-26. DOI: 10.1016/S1474-4422(04)00707-0. View

Beckman K, Ames B . The free radical theory of aging matures. Physiol Rev. 1998; 78(2):547-81. DOI: 10.1152/physrev.1998.78.2.547. View

Karlstrom H, Bergman A, Lendahl U, Naslund J, Lundkvist J . A sensitive and quantitative assay for measuring cleavage of presenilin substrates. J Biol Chem. 2001; 277(9):6763-6. DOI: 10.1074/jbc.C100649200. View

10.

Tang K, Wang C, Shen C, Sheng S, Ravid R, Jing N . Identification of a novel alternative splicing isoform of human amyloid precursor protein gene, APP639. Eur J Neurosci. 2003; 18(1):102-8. DOI: 10.1046/j.1460-9568.2003.02731.x. View

11.

Oleinik N, Krupenko N, Krupenko S . Cooperation between JNK1 and JNK2 in activation of p53 apoptotic pathway. Oncogene. 2007; 26(51):7222-30. DOI: 10.1038/sj.onc.1210526. View

12.

Zhou Y, Suram A, Venugopal C, Prakasam A, Lin S, Su Y . Geranylgeranyl pyrophosphate stimulates gamma-secretase to increase the generation of Abeta and APP-CTFgamma. FASEB J. 2007; 22(1):47-54. PMC: 2859886. DOI: 10.1096/fj.07-8175com. View

13.

Schallreuter K, Moore J, Wood J, Beazley W, Gaze D, Tobin D . In vivo and in vitro evidence for hydrogen peroxide (H2O2) accumulation in the epidermis of patients with vitiligo and its successful removal by a UVB-activated pseudocatalase. J Investig Dermatol Symp Proc. 1999; 4(1):91-6. DOI: 10.1038/sj.jidsp.5640189. View

14.

Skovronsky D, Moore D, Milla M, Doms R, Lee V . Protein kinase C-dependent alpha-secretase competes with beta-secretase for cleavage of amyloid-beta precursor protein in the trans-golgi network. J Biol Chem. 2000; 275(4):2568-75. DOI: 10.1074/jbc.275.4.2568. View

15.

Zhu X, Raina A, Rottkamp C, Aliev G, Perry G, Boux H . Activation and redistribution of c-jun N-terminal kinase/stress activated protein kinase in degenerating neurons in Alzheimer's disease. J Neurochem. 2001; 76(2):435-41. DOI: 10.1046/j.1471-4159.2001.00046.x. View

16.

Swatton J, Sellers L, Faull R, Holland A, Iritani S, Bahn S . Increased MAP kinase activity in Alzheimer's and Down syndrome but not in schizophrenia human brain. Eur J Neurosci. 2004; 19(10):2711-9. DOI: 10.1111/j.0953-816X.2004.03365.x. View

17.

Edbauer D, Winkler E, Regula J, Pesold B, Steiner H, Haass C . Reconstitution of gamma-secretase activity. Nat Cell Biol. 2003; 5(5):486-8. DOI: 10.1038/ncb960. View

18.

Tamagno E, Bardini P, Obbili A, Vitali A, Borghi R, Zaccheo D . Oxidative stress increases expression and activity of BACE in NT2 neurons. Neurobiol Dis. 2002; 10(3):279-88. DOI: 10.1006/nbdi.2002.0515. View

19.

Tong Y, Zhou W, Fung V, Christensen M, Qing H, Sun X . Oxidative stress potentiates BACE1 gene expression and Abeta generation. J Neural Transm (Vienna). 2004; 112(3):455-69. DOI: 10.1007/s00702-004-0255-3. View

20.

Xie Z, Dong Y, Maeda U, Moir R, Xia W, Culley D . The inhalation anesthetic isoflurane induces a vicious cycle of apoptosis and amyloid beta-protein accumulation. J Neurosci. 2007; 27(6):1247-54. PMC: 6673586. DOI: 10.1523/JNEUROSCI.5320-06.2007. View