Rabbit Anti-Mouse HO-1 (a.a. 1-266) Polyclonal antibody

The transcription factor nuclear factor erythroid 2-like 2 (NFE2L2) is essential for preventing type 2 diabetes mellitus (T2DM)-induced complications in animal models. This case and control study assessed genetic variants of NFE2L2 for associations with T2DM and its complications in Han Chinese volunteers. T2DM patients with (n=214) or without (n=236) complications, or healthy controls (n=359), were genotyped for six NFE2L2 single nucleotide polymorphisms (SNPs: rs2364723, rs13001694, rs10497511, rs1806649, rs1962142 and rs6726395) with TaqMan Pre-Designed SNP Genotyping and Sequence System. Serum levels of heme oxygenase-1 (HMOX1) were determined through enzyme-linked immunosorbent assay. Informative data were obtained for 341 cases and 266 controls. Between T2DM patients and controls, the genotypic and allelic frequencies and haplotypes of the SNPs were similar. However, there was a significant difference in genotypic and allelic frequencies of rs2364723, rs10497511, rs1962142 and rs6726395 between T2DM patients with and without complications, including peripheral neuropathy, nephropathy, retinopathy, foot ulcers and microangiopathy. Furthermore, HMOX1 levels were significantly higher in T2DM patients with complications than in controls. Multiple logistic regression analysis, however, showed that only rs2364723 significantly reduced levels of serum HMOX1 in T2DM patients for the GG genotype carriers compared with participants with CG+CC genotype. The data suggest that although NFE2L2 rs2364723, rs10497511, rs1962142 and rs6726395 were not associated with T2DM risk, they were significantly associated with complications of T2DM. In addition, only for rs2364723 higher serum HMOX1 levels were found in the T2DM patients with CG+CC than those with GG genotype.

Hair cell (HC) degeneration causes hearing loss in millions of people worldwide. Aminoglycoside exposure is one major cause of sensory HC damage. Aminoglycosides generate free radicals within the inner ear, permanently damaging sensory cells, and thus causing hearing loss. Hearing protection requires strategies to overcome the apparently irreversible loss of HCs in mammals. The nuclear factor of activated T cells (NFAT) inhibitor 11R-VIVIT reportedly protects HCs from gentamicin toxicity. Here we investigated whether the combination of 11R-VIVIT with the antioxidant L-carnitine or N-acetylcysteine could protect mouse cochlear HCs from gentamicin damage. Compared to single-component treatment, combined treatment with 11R-VIVIT plus L-carnitine yielded significant protection from gentamicin, and 11R-VIVIT plus N-acetylcysteine provided almost complete protection of HCs from gentamicin. Caspase activity in organ of Corti was significantly reduced by combined treatment with 11R-VIVIT + N-acetylcysteine + gentamicin, compared to 11R-VIVIT + gentamicin or gentamicin alone. Analysis of relative gene expression by qPCR revealed down-regulation of the pro-apoptotic genes Fasl and Casp9, and up-regulation of the antioxidant genes Hmox1 and Nrf2 after treatment with 11R-VIVIT + N-acetylcysteine + gentamicin, compared to single-compound treatment or gentamicin alone in cultures. Selective NFAT inhibition by 11R-VIVIT may be a good strategy for preventing gentamicin-induced HC damage. L-carnitine and N-acetylcysteine, with their ROS-reducing properties, contribute to the synergistic effectiveness with 11R-VIVIT by decreasing ROS-induced NFAT translocation. Our data suggest that a combined approach of NFAT inhibition together with an antioxidant, like N-acetylcysteine, could be useful for hearing loss treatment and/or prevention.