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Effect of Xixin decoction on phosphorylation toxicity at specific sites of tau protein in brains of rats with sporadic Alzheimer disease

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Journal of Traditional Chinese Medicine 2013年第6期33卷 787-793页

作者： Yongchang Diwu Jinzhou Tian Jing Shi First Clinical Medical College Encephalopathy of Shaanxi University of Chinese Medicine First Clinical Medical College Geriatrics of Beijing University of Chinese Medicine

OBJECTIVE: To explore the mechanism of action of Xixin decoction(XXD) for the prevention and treatment of sporadic Alzheimer disease(SAD) by investigating the effects of XXD on the phosphorylation of Thr231 and Ser422 sites of tau protein. METHODS: Specific pathogen-free(SPF) male Sprague-Dawley(SD) rats with SAD were randomly divided into six groups: sham-operated, model(intracerebroventricular injection of Streptozotocin, ICV-STZ), donepezil(0.92 mg/kg), XXD low-dose(7.61 g/kg-1 ·d-1), moderate-dose(15.21 g/kg-1 ·d-1), and high-dose(30.42 g/kg-1 ·d-1). Immunohistochemistry and western immunoblotting were used to detect the phosphorylation at Thr231 and Ser422 sites of tau protein. RESULTS: XXD different dose groups decreased to varying degrees the expression of phosphorylated tau at P-Thr231 and P-Ser422 sites in the hippocam-pus of SAD rats. No significant difference was found between the donepezil and model group. CONCLUSION: XXD may prevent SAD pathological progress by inhibiting hyperphosphorylation at the key sites of tau proteins.

关键词： Alzheimer disease Tau proteins phos-phorylation Xixin decoction

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Ion channelopathy and hyperphosphorylation contributing to cardiac arrhythmias~1

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Acta Pharmacologica Sinica 2005年第8期26卷 918-925页

作者： Feng YU Research Division of Pharmacology China Pharmaceutical University Nanjing 210009 China

The occurrence of cardiac an-hythmias is related to the abnormality of ion chan-nels not only in sarcolemma but also in the sarcoplasmic reticulum, which regu-lates the process of calcium release and up-take intracellularly. Patterns of ion channelopathy in the sarcolemma can be divided into single channel disorder from gene mutations and multiple channels disorder in a diseased hypertrophied heart. Abnormal RyR2, FKBP12.6, SERCA2a, and PLB are also involved in the initiation of cardiac arrhythmias. Maladjustment by hyperphosphorylation on the ion channels in the sarcolemma and RyR2-FKBP12.6 and SERCA2a-PLB is discussed. Hyperphosphorylation, which is the main abnormality upstream to ion channels, can be targeted for suppressing the deterioration of ion channelopathy in terms of new drug discovery in the treatment and prevention of malignant cardiac arrhythmias.

关键词： ion channels arrhythmia ryanodine receptor calcium release channel FKBP12.6 sarco-plasmic reticulum, phospholamban phos-phorylation

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