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Neuroprotective effects of neurokinin receptor one in dopaminergic neurons are mediated through Akt/PKB cell signaling pathway

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Název: Neuroprotective effects of neurokinin receptor one in dopaminergic neurons are mediated through Akt/PKB cell signaling pathway
Autoři: Chen, LW, Yung, KKL, Chan, YS, Chu, JMT
Zdroj: Neuropharmacology. 61:1389-1398
Informace o vydavateli: Elsevier BV, 2011.
Rok vydání: 2011
Témata: Male, 0301 basic medicine, Dopamine Agonists - Pharmacology, Time Factors, Apomorphine, Neuroblastoma - Pathology, Gene Expression Regulation - Drug Effects, Rats, Sprague-Dawley, Neuroblastoma, Neurokinin-1 Receptor Antagonists, Pyrrolidonecarboxylic Acid - Analogs & Derivatives - Therapeutic Use, Receptors, Drug Interactions, Peptide Fragments - Therapeutic Use, Enzyme Inhibitors, Oxidopamine - Toxicity, 0303 health sciences, Tumor, Cell Death, Caspase 3, Tyrosine 3-Monooxygenase - Metabolism, 3. Good health, Neuroprotective Agents, L-Lactate Dehydrogenase - Metabolism, Dopamine Agonists, Drug, Neurokinin-1 - Agonists - Antagonists & Inhibitors - Metabolism, Cell Death - Drug Effects, Corpus Striatum - Drug Effects - Pathology, Dopaminergic Neurons - Drug Effects - Physiology, Enzyme Inhibitors - Pharmacology, Caspase 3 - Metabolism, Bcl-Associated Death Protein - Metabolism, Motor Activity, Sympatholytics - Toxicity, Cell Line, Neuroprotective Agents - Therapeutic Use, Dose-Response Relationship, 03 medical and health sciences, Cell Line, Tumor, Analysis Of Variance, Animals, Apomorphine - Pharmacology, Neurotoxicity Syndromes - Etiology - Pathology - Physiopathology - Prevention & Control, Analysis of Variance, Dose-Response Relationship, Drug, L-Lactate Dehydrogenase, Animal, Substance P - Analogs & Derivatives - Therapeutic Use, Dopaminergic Neurons, Signal Transduction - Drug Effects - Physiology, Receptors, Neurokinin-1 - Agonists - Antagonists & Inhibitors - Metabolism, Corpus Striatum, Proto-Oncogene Proteins C-Akt - Metabolism, Rats, Disease Models, Animal, Gene Expression Regulation, Rotarod Performance Test, Disease Models, Sprague-Dawley
Popis: Neurokinin one (NK1) receptor is Substance P (SP) receptor and it is abundantly distributed in the basal ganglia. Growing evidences were shown on their possible roles in the pathogenesis and treatment of Parkinson's disease (PD). NK1 receptor is a kind of G-protein-coupled-receptor (GPCR) and it links to various downstream survival signaling pathways. In the present study, treatment of NK1 receptor agonist septide [(Pyr6, Pro9)-SP (6-11)] was found to ameliorate the motor deficit in 6-hydroxydopamine (6-OHDA) lesioned rats in apomorphine rotation test. Septide treatments were also demonstrated to provide neuroprotection. In 6-OHDA lesioned rats, protection of TH immunoreactive neurons and terminals in substantia nigra (SN) and striatum was found after septide treatment. In SH-SY5Y cultures, cytotoxicity of 6-OHDA was reduced by septide pretreatment. In addition, up-regulations of phosphorylated serine-threonine kinase Akt and phosphorylated mitochondrial apoptotic protein BAD were observed in both in vivo and in vitro models, indicating the inhibition of apoptotic pathway by septide. In conclusion, septide could trigger the pro-survival Akt/PKB signaling pathway and protect dopaminergic neurons in in vivo and in vitro models against 6-OHDA toxicity. Therefore septide treatment may have therapeutic implications in treatment of PD.
Druh dokumentu: Article
Jazyk: English
ISSN: 0028-3908
DOI: 10.1016/j.neuropharm.2011.08.027
Přístupová URL adresa: https://pubmed.ncbi.nlm.nih.gov/21907219
https://pubmed.ncbi.nlm.nih.gov/21907219/
http://hub.hku.hk/handle/10722/171786
https://core.ac.uk/display/37999291
https://www.ncbi.nlm.nih.gov/pubmed/21907219
https://scholars.hkbu.edu.hk/en/publications/neuroprotective-effects-of-neurokinin-receptor-one-in-dopaminergi-2
http://www.sciencedirect.com/science/article/pii/S0028390811003601
http://hdl.handle.net/10722/171786
Rights: Elsevier TDM
Přístupové číslo: edsair.doi.dedup.....1313724bdd75495a0ab60b0d3fd2963c
Databáze: OpenAIRE
Popis
Abstrakt:Neurokinin one (NK1) receptor is Substance P (SP) receptor and it is abundantly distributed in the basal ganglia. Growing evidences were shown on their possible roles in the pathogenesis and treatment of Parkinson's disease (PD). NK1 receptor is a kind of G-protein-coupled-receptor (GPCR) and it links to various downstream survival signaling pathways. In the present study, treatment of NK1 receptor agonist septide [(Pyr6, Pro9)-SP (6-11)] was found to ameliorate the motor deficit in 6-hydroxydopamine (6-OHDA) lesioned rats in apomorphine rotation test. Septide treatments were also demonstrated to provide neuroprotection. In 6-OHDA lesioned rats, protection of TH immunoreactive neurons and terminals in substantia nigra (SN) and striatum was found after septide treatment. In SH-SY5Y cultures, cytotoxicity of 6-OHDA was reduced by septide pretreatment. In addition, up-regulations of phosphorylated serine-threonine kinase Akt and phosphorylated mitochondrial apoptotic protein BAD were observed in both in vivo and in vitro models, indicating the inhibition of apoptotic pathway by septide. In conclusion, septide could trigger the pro-survival Akt/PKB signaling pathway and protect dopaminergic neurons in in vivo and in vitro models against 6-OHDA toxicity. Therefore septide treatment may have therapeutic implications in treatment of PD.
ISSN:00283908
DOI:10.1016/j.neuropharm.2011.08.027