Janus Kinase 2, an Early Target of α7 Nicotinic Acetylcholine Receptor-mediated Neuroprotection against Aβ-(1–42) Amyloid
作者： Seán Shaw , Merouane Bencherif , Mario B. Marrero
关键词:
摘要: The molecular mechanisms of α7 nicotinic acetylcholine receptor (nAChR)-mediated neuroprotection remain unclear. In this study we provide evidence that nicotine stimulation nAChR transduces signals to phosphatidylinositol 3-kinase and Akt via Janus kinase 2 (JAK2) in a cascade, which results neuroprotection. Exposure β-amyloid the activation apoptotic enzyme caspase-3 cleavage DNA-repairing poly-(ADP-ribose) polymerase. This cascade is inhibited by through JAK2 activation, these effects are blocked preincubation with JAK2-specific inhibitor AG-490. We also found pretreatment cells angiotensin II blocks nicotine-induced AT2 completely prevents nAChR-mediated neuroprotective further suggesting pivotal role for JAK2. These findings identify novel interactions relevant neuronal viability suggest therapeutic strategies optimize
elsevier.com
sci-hub.se 参考文章(22)
Murat Digicaylioglu, Stuart A. Lipton, Erythropoietin-mediated neuroprotection involves cross-talk between Jak2 and NF-κB signalling cascades Nature. ,vol. 412, pp. 641- 647 ,(2001) , 10.1038/35088074
Takeshi Kihara, Shun Shimohama, Hideyuki Sawada, Kazuhiro Honda, Tomoki Nakamizo, Hiroshi Shibasaki, Toshiaki Kume, Akinori Akaike, α7 Nicotinic Receptor Transduces Signals to Phosphatidylinositol 3-Kinase to Block A β-Amyloid-induced Neurotoxicity Journal of Biological Chemistry. ,vol. 276, pp. 13541- 13546 ,(2001) , 10.1074/JBC.M008035200
Kelly T Dineley, Marcus Westerman, Duy Bui, Karen Bell, Karen Hsiao Ashe, J David Sweatt, None, β-Amyloid Activates the Mitogen-Activated Protein Kinase Cascade via Hippocampal α7 Nicotinic Acetylcholine Receptors:In Vitro and In Vivo Mechanisms Related to Alzheimer's Disease The Journal of Neuroscience. ,vol. 21, pp. 4125- 4133 ,(2001) , 10.1523/JNEUROSCI.21-12-04125.2001
Kotaro Kumano, Atsuhito Nakao, Hiroshi Nakajima, Satoshi Miike, Kazuhiro Kurasawa, Yasushi Saito, Itsuo Iwamoto, Blockade of JAK2 by tyrphostin AG-490 inhibits antigen-induced eosinophil recruitment into the mouse airways. Biochemical and Biophysical Research Communications. ,vol. 270, pp. 209- 214 ,(2000) , 10.1006/BBRC.2000.2403
R E Ryan, S A Ross, J Drago, R E Loiacono, Dose-related neuroprotective effects of chronic nicotine in 6-hydroxydopamine treated rats, and loss of neuroprotection in α4 nicotinic receptor subunit knockout mice British Journal of Pharmacology. ,vol. 132, pp. 1650- 1656 ,(2001) , 10.1038/SJ.BJP.0703989
William R Kem, The brain α7 nicotinic receptor may be an important therapeutic target for the treatment of Alzheimer's disease: studies with DMXBA (GTS-21) Behavioural Brain Research. ,vol. 113, pp. 169- 181 ,(2000) , 10.1016/S0166-4328(00)00211-4
Jennifer Court, Carmen Martin-Ruiz, Margaret Piggott, Dean Spurden, Martin Griffiths, Elaine Perry, Nicotinic receptor abnormalities in Alzheimer's disease. Biological Psychiatry. ,vol. 49, pp. 175- 184 ,(2001) , 10.1016/S0006-3223(00)01116-1
Eleni Dicou, Samir Attoub, Pierre Gressens, None, Neuroprotective effects of leptin in vivo and in vitro. Neuroreport. ,vol. 12, pp. 3947- 3951 ,(2001) , 10.1097/00001756-200112210-00019
S Negoro, Activation of JAK/STAT pathway transduces cytoprotective signal in rat acute myocardial infarction. Cardiovascular Research. ,vol. 47, pp. 797- 805 ,(2000) , 10.1016/S0008-6363(00)00138-3
Ikuya Sakai, Andrew S. Kraft, The kinase domain of Jak2 mediates induction of Bcl-2 and delays cell death in hematopoietic cells Journal of Biological Chemistry. ,vol. 272, pp. 12350- 12358 ,(1997) , 10.1074/JBC.272.19.12350