楔红抑制吗啡诱导的神经母细胞瘤细胞的细胞适应。

Noor Azuin Suliman, M. Moklas, C. N. M. Taib, Mohamad Taufik Hidayat Baharuldin, S. M. Chiroma
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引用次数: 1

摘要

背景:慢性吗啡刺激阿片受体,特别是微阿片亚型(MOR)的长时间刺激,这反过来标志着细胞适应。然而,长期服用吗啡后突然停止使用会引起戒断综合征。因此,本研究旨在寻找一种吗啡戒断的替代治疗方法,即利用cuneatum (E. cuneatum)红叶生物碱提取物对吗啡暴露的神经母细胞瘤细胞系进行治疗。方法ssk - n - sh是一种商业化的神经母细胞瘤细胞系,在两个独立的研究设计中使用;吗啡的拮抗和预处理。拮抗处理采用吗啡与虎牙鼠或吗啡与美沙酮同时作用24 h的方法。预处理设计采用吗啡作用24 h,再分别作用虎牙鼠或美沙酮24 h的方法。收集细胞质部分,进行与细胞适应有关的蛋白表达;丝裂原活化蛋白(MAP)/细胞外信号调节(ERK)激酶1/2 (MEK 1/2)、细胞外信号调节激酶2 (ERK 2)、camp依赖性蛋白激酶(PKA)和蛋白激酶C (PKC)。结果在拮抗组,吗啡联合虎突治疗小鼠MEK 1/2、ERK 2、PKA、PKC水平与吗啡联合美沙酮相当。吗啡预处理后的神经母细胞瘤细胞MEK 1/2、ERK 2、PKA和PKC表达水平较高,而cunetatum和美沙酮预处理后的神经母细胞瘤细胞适应蛋白表达水平正常。Cuneatum通过降低细胞适应蛋白水平发挥抗成瘾特性,其效果与美沙酮(一种公认的抗成瘾药物)相当。
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Erythroxylum cuneatum prevented cellular adaptation in morphine-induced neuroblastoma cells.
BACKGROUND Chronic morphine stimulates prolonged stimulation of opioid receptors, especially µ-opioid subtype (MOR), which in turn signals cellular adaptation. However, the sudden termination of morphine after chronic intake causes withdrawal syndrome. OBJECTIVES Hence, this study was designed to find an alternative treatment for the morphine withdrawal using the alkaloid leaf extract of Erythroxylum cuneatum (E. cuneatum), done on morphine-exposed neuroblastoma cell lines. METHODS SK-N-SH, a commercialised neuroblastoma cell line, was used in two separate study designs; the antagonistic and pre-treatment of morphine. The antagonistic treatment was conducted through concurrent exposure of the cells to morphine and E. cuneatum or morphine and methadone for 24 h. The pre-treatment design was carried out by exposing the cells to morphine for 24 h, followed by 24 h exposures to E. cuneatum or methadone. The cytosolic fraction was collected and run for protein expression involved in cellular adaptation; mitogen-activated protein (MAP)/extracellular signal-regulated (ERK) kinase 1/2 (MEK 1/2), extracellular signal-regulated kinase 2 (ERK 2), cAMP-dependent protein kinase (PKA) and protein kinases C (PKC). RESULTS The antagonistic treatment showed the normal level of MEK 1/2, ERK 2, PKA and PKC by the combination treatment of morphine and E. cuneatum, comparable to the combination of morphine and methadone. Neuroblastoma cells exposed to morphine pre-treatment expressed a high level of MEK 1/2, ERK 2, PKA and PKC, while the treatments with E. cuneatum and methadone normalised the expression of the cellular adaptation proteins. CONCLUSION E. cuneatum exerted anti-addiction properties by lowering the levels of cellular adaptation proteins, and its effects are comparable to that of methadone (an established anti-addiction drug).
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来源期刊
Central nervous system agents in medicinal chemistry
Central nervous system agents in medicinal chemistry Psychology-Neuropsychology and Physiological Psychology
CiteScore
2.10
自引率
0.00%
发文量
21
期刊介绍: Central Nervous System Agents in Medicinal Chemistry aims to cover all the latest and outstanding developments in medicinal chemistry and rational drug design for the discovery of new central nervous system agents. Containing a series of timely in-depth reviews written by leaders in the field covering a range of current topics, Central Nervous System Agents in Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments in the field.
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