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Related Research on Morphine and Thioredoxin

Author: FengYueMei
Tutor: BaiJie
School: Kunming University of Science and Technology
Course: Biochemistry and Molecular Biology
Keywords: Morphine Thioredoxin Cyclin -dependent protein kinase -5 Drug Addiction
CLC: R749.6
Type: Master's thesis
Year: 2009
Downloads: 24
Quote: 0
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Abstract


Currently, drug addiction has become a huge social and health problems afflicting humankind. Drug addiction is generated by drug abuse and the brain's reward system interaction chronic, relapsing brain disease, mainly compulsive drug symptoms and persistent craving state. And drug addiction related brain regions: the prefrontal cortex, hippocampus, locus coeruleus, nucleus accumbens, amygdala, striatum, caudate nucleus. The study found that the presence of the redox state of equilibrium imbalance during the development of opioid drug addiction. At the same time, the application of proteomics methods in recent years, also found that the presence of oxidative stress related proteins change in opioid drug addiction process. Thioredoxin (Thioredoxin, Trx) is an important protein for regulating oxidative stress is a widely present in the low molecular weight proteins in prokaryotic and eukaryotic cells, which contains the conserved active site Cys-Gly-Pro-Cys, as a pleiotropic cytokine with important biological functions. Trx gene expression regulatory sequences found by: Antioxidant response element, cAMP response A element (cAMP responsive element, CRE) and a plurality of SP-1 binding sites in their regulatory sequences. A molecular basis for opioid drug addiction can lead to the upregulation of the cAMP activate CREB, caused by altered expression of drug addiction-related genes (such as of BDNF, CDK5, GDNF, t-PA, etc.). These features provide a study for us to study the molecular mechanisms of drug addiction assumptions. For more and more drug addiction, the Trx and addiction relationship has not been reported. Neuroblastoma tumor cells SH-SY5Y study explored the influence of morphine Trx expression from the cellular level, the results prove 20μM morphine-induced Trx expression in a dose-dependent; morphine for Trx expression the impact also has a time-dependent manner, is enabled whenever TRx the expression in 1-3 h by a significant inhibition at 6-24 h to give the reply and gradually elevated; PI3K inhibitor LY294002 inhibited the expression of Trx; Add GSK3β inhibition agent LiCl reduced Trx expression to get a reply; adding naloxone, a morphine-induced Trx expression; the morphine withdrawal 1 h, 2 h, 3 h, 4 h enables increased Trx expression reverts to control group level. Studies have shown that the cyclin-dependent protein kinase 5 (cyclin dependent kinases-5, Cdk5) has an important regulatory role in the addiction process. Therefore, in the present study, we also detected the expression of CDK5. The study found that the role of morphine, CDK5 showed the same trend with Trx. LY294002 inhibits CDK5 expression; LiCl can reduce the expression of CDK5 get replies; adding naloxone blocked the expression of morphine-induced CDK5; morphine withdrawal 1 h, 2 h, 3 h, 4 h so that increased CDK5 expression returned to the level of the control group. In summary, this study demonstrated that the morphine-induced Trx expression in a dose-dependent and time-dependent characteristics to clarify the signaling pathway of morphine induced Trx expression. Interestingly, the morphine CDK5 expression the Trx same trend was found in the present study. These results are more fully explained Trx may be involved in the occurrence and development of addiction. Therefore, Trx is an important target molecule of drug addiction.

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