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Palmatine Inhibits Up-Regulation of GRP78 and CALR Protein in an STZ-Induced Diabetic Rat Model
Current Pharmaceutical Biotechnology ( IF 2.8 ) Pub Date : 2021-01-31 , DOI: 10.2174/1389201021666200730124208
Patrick N Okechukwu 1 , Sophia O Ekeuku 1 , Hor K Chan 1 , Kalpana Eluri 2 , Gabriele R A Froemming 3
Affiliation  

Background: Diabetes Mellitus (DM) is characterized by hyperglycemia (high blood glucose levels) which is due to the destruction of insulin-producing β-cells in the islets of Langerhans in the pancreas. It is associated with oxidative and endoplasmic reticulum stress. The plant alkaloid Palmatine has been previously reported to possess antidiabetic and antioxidant properties as well as other protective properties against kidney and liver tissue damage.

Objective: Here, we investigated the ability of Palmatine to reduce the up-regulation of chaperone proteins Glucose Regulatory Protein 78 (GRP78), and Calreticulin (CALR) protein in a Streptozotocin (STZ)-induced diabetic rat model.

Methods: Streptozotocin (STZ) induced diabetes in Sprague Dawley rats treated with 2mg/kg of Palmatine for 12 weeks after the elevation of plasma glucose levels above 11mmol/L post-STZ administration. Proteins were extracted from the pancreas after treatment and Two-Dimensional gel electrophoresis (2-DE), PDQuest 2-D analysis software genomic solutions and mass spectrometer were used to analyze differentially expressed protein. Mass Spectrometry (MS/MS), Multidimensional Protein Identification Technology (MudPIT) was used for protein identification.

Results: There was an up-regulation of the expression of chaperone proteins CALR and GRP78 and down-regulation of the expression of antioxidant and protection proteins peroxidoxin 4 (Prdx4), protein disulfide isomerase (PDIA2/3), Glutathione-S-Transferase (GSTs), and Serum Albumin (ALB) in non-diabetic rats. Palmatine treatment down-regulated the expression of chaperone proteins CALR and GRP78 and up-regulated the expression of Prdx4, PDIA2/3, GST, and ALB.

Conclusion: Palmatine may have activated antioxidant proteins, which protected the cells against reactive oxygen species and endoplasmic stress. The result is in consonance with our previous report on Palmatine.



中文翻译:

巴马汀抑制STZ诱导的糖尿病大鼠模型中GRP78和CALR蛋白的上调。

背景:糖尿病(DM)的特征是高血糖症(高血糖水平),这是由于胰腺Langerhans胰岛中产生胰岛素的β细胞被破坏所致。它与氧化和内质网应激有关。先前已经报道了植物生物碱棕榈碱具有抗糖尿病和抗氧化特性,以及针对肾脏和肝脏组织损伤的其他保护特性。

目的:在这里,我们研究了帕拉帕汀在链脲佐菌素(STZ)诱导的糖尿病大鼠模型中减少伴侣蛋白葡萄糖调节蛋白78(GRP78)和钙网蛋白(CALR)蛋白上调的能力。

方法:在STZ给药后血浆葡萄糖水平升高至超过11mmol / L后,链脲佐菌素(STZ)诱导的Sprague Dawley大鼠糖尿病接受2mg / kg的棕榈碱治疗12周。处理后从胰腺中提取蛋白质,并使用二维凝胶电泳(2-DE),PDQuest 2-D分析软件基因组溶液和质谱仪分析差异表达的蛋白质。质谱(MS / MS),多维蛋白质鉴定技术(MudPIT)用于蛋白质鉴定。

结果:伴侣蛋白CALR和GRP78的表达上调,抗氧化剂和保护蛋白过氧化物酶4(Prdx4),蛋白二硫键异构酶(PDIA2 / 3),谷胱甘肽-S-转移酶( GSTs和非糖尿病大鼠的血清白蛋白(ALB)。棕榈碱处理下调伴侣蛋白CALR和GRP78的表达,并上调Prdx4,PDIA2 / 3,GST和ALB的表达。

结论:棕榈碱可能具有激活的抗氧化剂蛋白,可以保护细胞免受活性氧和内质应激的侵害。结果与我们先前关于Palmatine的报告相吻合。

更新日期:2021-03-29
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