Association of biliverdin reductase A gene polymorphisms with neonatal hyperbilirubinemia from Fujian area / 中华实用儿科临床杂志

Objective To assess the association of single nucleotide polymorphisms (SNPs)of biliverdin reductase A (BLVRA) with neonatal hyperbilirubinemia from Fujian area.Methods A total of 286 patients with neonatal hyperbilirubinemia and 250 healthy controls were enrolled.Genotypes of 5 SNPs within BLVRA gene including rs699512,rs1802846,rs7738,rs1637530 and rs2302032 were determined with matrix-assisted laser desorption ionization/time of flight mass spectrometer.The frequencies of genotype,allele,haplotype and their differentiations were analyzed.Results All 5 SNPs had conformed to Hardy-Weinberg equilibrium (all P ＞ 0.05).rs699512 and rs1637530 showed a significant difference between the 2 groups in both allelic and genotypic frequencies (all P ＜ 0.05),but no significant differences were found in the other SNPs(all P ＞ O.05).In recessive model,the frequency of rs699512 GG genotype of patients was significantly lower than that of the healthy control group(OR =0.494,95％ CI:0.276-0.886,P =0.018),while in dominant model,the frequencies of rs699512 GG + AG and rs1637530 TT + CT genotype of patients were significantly lower than that of the healthy control group(OR =0.678,0.627;95％ CI:0.482-0.954,0.444-0.885;P =0.026,0.008).Based on linkage disequilibrium analysis and haplotype construction,rs1637530,rs2302032,rs699512 and rs1802846 locus in the same area.Based on haplotype CGAT,TGGT,CTAT and CGGT had significant differences between the 2 groups (all P ＜ 0.05),and could reduce the risk of high blood bilirubin (OR =0.588,0.687,0.501;95％ CI:0.434-0.797,0.496-0.952,0.250-1.004).Conclusions rs699512 and rs1637530 may be associated with neonatal hyperbilirubinemia,A allele in rs699512 and C allele in rs1637530 may be associated with significantly increased risk of neonatal hyperbilirubinemia.

Biliverdin reductase A in the prevention of cellular senescence against oxidative stress

Biliverdin reductase A (BLVRA), an enzyme that converts biliverdin to bilirubin, has recently emerged as a key regulator of the cellular redox cycle. However, the role of BLVRA in the aging process remains unclear. To study the role of BLVRA in the aging process, we compared the stress responses of young and senescent human diploid fibroblasts (HDFs) to the reactive oxygen species (ROS) inducer, hydrogen peroxide (H2O2). H2O2 markedly induced BLVRA activity in young HDFs, but not in senescent HDFs. Additionally, depletion of BLVRA reduced the H2O2-dependent induction of heme oxygenase-1 (HO-1) in young HDFs, but not in senescent cells, suggesting an aging-dependent differential modulation of responses to oxidative stress. The role of BLVRA in the regulation of cellular senescence was confirmed when lentiviral RNAitransfected stable primary HDFs with reduced BLVRA expression showed upregulation of the CDK inhibitor family members p16, p53, and p21, followed by cell cycle arrest in G0-G1 phase with high expression of senescence-associated beta-galactosidase. Taken together, these data support the notion that BLVRA contributes significantly to modulation of the aging process by adjusting the cellular oxidative status.

Effects of echinacoside on protein expression from substantia nigra and striatal tissue in mouse MPTP model of Parkinsons disease by using 2-dimensional electrophoresis analysis / 中国药理学通报

Aim To study the effect of echinacoside on behavior and proteins expression from substantia nigra and striatal tissue in MPTP mouse model of Parkinsons disease(PD)and discover the mechanism of its potential dopaminergic neuroprotective effect in the protein level.Methods The mouse model of PD was induced by 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)and the behavioral analysis of C57BL/6 mice was performed by using spontaneous movement and rotarod test.A proteomic approach based on 2-dimensional electrophoresis(2-DE),mass spectrometry(MS)and figure analysis was used to evaluate the effect of echinacoside on the behavior and the protein expression in substantia nigra and striatal tissue in C57BL/6 mice after MPTP administration.Results ① Compared with control,MPTP lesion significantly reduced the number of spontaneous movement and latent period of mice on the rotating rod(both P