Transgenerational Effects of Arsenic Exposure on Learning and Memory in Rats: Crosstalk between Arsenic Methylation, Hippocampal Metabolism, and Histone Modifications.

Arsenic (As) is widely present in the natural environment, and exposure to it can lead to learning and memory impairment. However, the underlying epigenetic mechanisms are still largely unclear. This study aimed to reveal the role of histone modifications in environmental levels of arsenic (sodium arsenite) exposure-induced learning and memory dysfunction in male rats, and the inter/transgenerational effects of paternal arsenic exposure were also investigated. It was found that arsenic exposure impaired the learning and memory ability of F0 rats and down-regulated the expression of cognition-related genes Bdnf, c-Fos, mGlur1, Nmdar1, and Gria2 in the hippocampus. We also observed that inorganic arsenite was methylated to DMA and histone modification-related metabolites were altered, contributing to the dysregulation of H3K4me1/2/3, H3K9me1/2/3, and H3K4ac in rat hippocampus after exposure. Therefore, it is suggested that arsenic methylation and hippocampal metabolism changes attenuated H3K4me1/2/3 and H3K4ac while enhancing H3K9me1/2/3, which repressed the key gene expressions, leading to cognitive impairment in rats exposed to arsenic. In addition, paternal arsenic exposure induced transgenerational effects of learning and memory disorder in F2 male rats through the regulation of H3K4me2 and H3K9me1/2/3, which inhibited c-Fos, mGlur1, and Nmdar1 expression. These results provide novel insights into the molecular mechanism of arsenic-induced neurotoxicity and highlight the risk of neurological deficits in offspring with paternal exposure to arsenic.

MiR-7, miR-9 and miR-375 contribute to effect of Exendin-4 on pancreatic ß-cells in high-fat-diet-fed mice.

PURPOSE: The purpose of this study was to test whether glucagon-like peptide-1 (GLP-1) receptor activation preserved pancreatic ß-cells via the regulation of microRNAs and target genes in high-fat-diet-fed mice. METHODS: C57BL/6 male mice were simultaneously treated with high-fat-diet (HFD) and GLP-1 analogue, Exendin-4 (Ex-4) (3 µg/kg/day or 30 µg/kg/day), i.p. or vehicle, for consecutive 13 weeks. Fasting blood glucose, postprandial blood glucose, ΔI30/ΔG30, HOMA-IR and HOMA-% ß were measured in each group. Pancreatic ß-cell mass was assessed by immunohistochemistry. The expression of miRNAs and related downstream genes were investigated using quantitative real-time PCR. RESULTS: Thirteen weeks of Ex-4 treatment significantly reduced body weight and food intake in HFD-fed mice (P.

GLP-1 contributes to increases in PGC-1α expression by downregulating miR-23a to reduce apoptosis.

GLP-1 can help to overcome problems of liver cells metabolism, not only pancreatic cell. But the explicit mechanism of this effect remains unclear. In recent years, microRNAs have received the attention of researchers and some microRNAs have important implications for diabetes. The mitochondrial protective gene PGC-1α is also closely related to diabetes, and UCP2 is related to anti-mitochondrial oxidative stress, but the mechanism of action of these genes is unclear. In this study, we used HepG2 cell line and used the cell counting kit (CCK) to measure the cell viability with GLP-1(7-36) and/or glucotoxicity. To investigate alterations in gene expression resulting from incubation with GLP-1 (7-36) or hyperglycaemia, the RNA expression levels of miR-23a, PGC-1α, Bak, Bax and UCP2 were quantified using real-time PCR. The protein levels of PGC-1α were determined by western blot. The role of miR-23a in the regulation of PGC-1α was further assessed through cell transfection to downregulate of miR-23a expression. In this study, the viability of HepG2 hepatocytes was decreased under hyperglycaemia, but incubation with 10 nmol/L GLP-1 (7-36) amide for 24 h significantly increased the viability and decreased the mRNA expression levels of Bax and Bak. Incubation with GLP-1(7-36) amide for 24 h attenuated the RNA expression of miR-23a and increased the mRNA and protein expression of PGC-1α. Inhibition of miR-23a expression by cell transfection led to increases in the mRNA and protein expression of PGC-1α. In addition, the mRNA expression of UCP2 increased after incubation with GLP-1(7-36) for 24 h. In conclusion, GLP-1 induced increased expression of mitochondrial protective gene PGC-1α by downregulating miR-23a to inhibit hepatocyte apoptosis and also enhanced UCP2 to reduce apoptosis.

Bacillus cereus NJ01 induces SA- and ABA-mediated immunity against bacterial pathogens through the EDS1-WRKY18 module.

Emerging evidence suggests a beneficial role of rhizobacteria in ameliorating plant disease resistance in an environment-friendly way. In this study, we characterize a rhizobacterium, Bacillus cereus NJ01, that enhances bacterial pathogen resistance in rice and Arabidopsis. Transcriptome analyses show that root inoculation of NJ01 induces the expression of salicylic acid (SA)- and abscisic acid (ABA)-related genes in Arabidopsis leaves. Genetic evidence showed that EDS1, PAD4, and WRKY18 are required for B. cereus NJ01-induced bacterial resistance. An EDS1-PAD4 complex interacts with WRKY18 and enhances its DNA binding activity. WRKY18 directly binds to the W box in the promoter region of the SA biosynthesis gene ICS1 and ABA biosynthesis genes NCED3 and NCED5 and contributes to the NJ01-induced bacterial resistance. Taken together, our findings indicate a role of the EDS1/PAD4-WRKY18 complex in rhizobacteria-induced disease resistance.

Polymorphisms in HIF-1a gene are not associated with diabetic retinopathy in China.

BACKGROUND: It has been reported that vascular endothelial growth factor (VEGF) is a susceptibility gene for both type 2 diabetes mellitus (T2DM) and diabetic retinopathy (DR). In response to hypoxia, VEGF mRNA levels are increased, which is mainly mediated by the binding of hypoxia-inducible factor-1 (HIF-1) and hypoxia response element upstream of the transcriptional start site of VEGF. Therefore, HIF-1a is supposed to be involved in pathology of DR. AIM: To investigate whether the polymorphisms in HIF-1a gene are associated with DR. METHODS: Two hundred and ninety-nine type 2 diabetic patients (128 males and 171 females) and 144 healthy volunteers were recruited. Mean age was 56.04 ± 21.05 years. According to the results of fundus fluorescein angiography and examination of ophthalmoscopy, patients were divided into two groups, DNR group (diabetes without retinopathy) and DR group (diabetes with retinopathy). There are 150 cases in DNR group and 149 cases in DR group. Two single nucleotide polymorphisms (SNP) of the HIF-1a gene were tested using matrix-assisted laser desorption/Ionization time of flight mass spectrometry. The frequency of genotypes and alleles, and odds ratio were measured. RESULTS: The mean age of the cases with diabetes was 55.84 ± 3.66 years, the mean age of the cases with DR was 55.97 ± 4.66 years and that of controls was 56.32 ± 4.70 years. Two variations were found in 76 patients. Rs11549465 is the change of C-T base, rs11549467 is the change of G-A base. The rs11549467 G/A genotype was 5.33% in diabetes and 6.04% in DR patients, respectively. The rs11549465 C/T genotype was 10% and 12.75% in patients with diabetes and DR. The rs11549467 A allele frequencies and rs11549465 T frequencies was similar to that of controls. Paired SNP linkage disequilibrium analysis indicated that rs11549467 was in linkage disequilibrium with rs11549465. Haplotype association analysis denoted that the haplotype association exhibited similar distribution in the patients compared to the normal controls. CONCLUSION: This study suggests that there is no relationship between the genetic variations of HIF1a and diabetes or DR.