Garlic (Allium sativum) increases SIRT1 and SIRT2 gene expressions in the kidney and liver tissues of STZ- and STZ+niacinamide-induced diabetic rats

Background Diabetic nephropathy and liver damage are important complications of diabetes mellitus (DM). Various factors, such as sirtuins (silent information regulators or SIRTs) are associated with these complications. Sirtuins are a family of NAD+-dependent proteins, and seven types of these can be found in mammalians. In this study, we evaluated the effects of aqueous garlic extract (G) on the expressions of SIRT1 and SIRT2 genes in the kidney and liver tissues of rats with types 1 and 2 diabetes. Methods A total of 36 male Wistar rats (230–280 g) were randomly divided into six groups: C: normal control rats, D1M: type 1 diabetic rats (induced with streptozotocin, STZ), D1M+G: type 1 diabetic rats that treated with garlic extract, D2M: type 2 diabetic rats (induced with STZ and niacinamide), D2M+G: type 2 diabetic rats treated with garlic extract, and G: normal rats that received garlic extract. At the end of the treatment time, kidney and liver tissue samples were collected from all rats. The SIRT1 and SIRT2 gene expressions were determined by qRT-PCR. Results The SIRT1 and SIRT2 gene expressions in the liver and kidney tissues of diabetic rats decreased significantly compared with those in the control rats (p<0.05). After treatment with garlic extract, the gene expressions also increased significantly compared with those in the diabetic rats and are close to normal level (p<0.05). Conclusions Garlic extract increased the SIRT1 and SIRT2 gene expressions in the livers and kidneys of diabetic rats. The antioxidant and anti-inflammatory effects of garlic have been proven in many studies. Thus, it is possible that garlic – with its effects on this pathway of gene expression – can have antioxidant and anti-inflammatory effects, thus decreasing diabetic complications.

miR-486-3p Influences the Neurotoxicity of a-Synuclein by Targeting the SIRT2 Gene and the Polymorphisms at Target Sites Contributing to Parkinson’s Disease

Background/Aims: Increasing evidence suggests the important role of sirtuin 2 (SIRT2) in the pathology of Parkinson’s disease (PD). However, the association between potential functional polymorphisms in the SIRT2 gene and PD still needs to be identified. Exploring the molecular mechanism underlying this potential association could also provide novel insights into the pathogenesis of this disorder. Methods: Bioinformatics analysis and screening were first performed to find potential microRNAs (miRNAs) that could target the SIRT2 gene, and molecular biology experiments were carried out to further identify the regulation between miRNA and SIRT2 and characterize the pivotal role of miRNA in PD models. Moreover, a clinical case-control study was performed with 304 PD patients and 312 healthy controls from the Chinese Han population to identify the possible association of single nucleotide polymorphisms (SNPs) within the miRNA binding sites of SIRT2 with the risk of PD. Results: Here, we demonstrate that miR-486-3p binds to the 3’ UTR of SIRT2 and influences the translation of SIRT2. MiR-486-3p mimics can decrease the level of SIRT2 and reduce a-synuclein (α-syn)-induced aggregation and toxicity, which may contribute to the progression of PD. Interestingly, we find that a SNP, rs2241703, may disrupt miR-486-3p binding sites in the 3’ UTR of SIRT2, subsequently influencing the translation of SIRT2. Through the clinical case-control study, we further verify that rs2241703 is associated with PD risk in the Chinese Han population. Conclusion: The present study confirms that the rs2241703 polymorphism in the SIRT2 gene is associated with PD in the Chinese Han population, provides the potential mechanism of the susceptibility locus in determining PD risk and reveals a potential target of miRNA for the treatment and prevention of PD.