MiR-133b-5p regulates the expression of the heat shock protein 70 during rat neuronal cell apoptosis induced by the gp120 V3 loop peptide.

Neuronal cell dysfunction and apoptosis, the main causes of HIV-associated dementia, and its underlying mechanism are important unsolved health problems. Many research reports suggest that miRNAs regulate HIV-1-induced apoptosis. We used the HIV-1 gp120 V3 Loop peptide to induce primary rat cortical neurons apoptosis. Next, we used a microRNA microarray to identify the significant changes of miRNA in the rat cortical neurons treated with the gp120 V3 loop peptide. We used western blot and real-time PCR to measure the regulation of heat shock protein 70 by rno-miR-133b-5p. In response to the gp120 V3 loop peptide treatment, rat cortical neurons exhibited 11 up-regulated and 21 down-regulated miRNAs. We further examined miR-133b-5p, a microRNA that was up-regulated more than 118-fold. In addition, both HSP70 mRNA and protein expression were dose-dependent in rats cortical neurons treated with gp120 V3 loop peptide for 48 hr. MiR-133b-5p could regulate heat shock protein 70 (HSP70) at both transcription and translation levels. Rno-miR-133b-5p might be less significant for the gp120 V3 loop peptide induced neuron apoptosis. Thus, we discovered a potential new target for the regulation of HIV-1 gp120- induced apoptosis.

Allosteric-activation mechanism of BK channel gating ring triggered by calcium ions.

Calcium ions bind at the gating ring which triggers the gating of BK channels. However, the allosteric mechanism by which Ca2+ regulates the gating of BK channels remains obscure. Here, we applied Molecular Dynamics (MD) and Targeted MD to the integrated gating ring of BK channels, and achieved the transition from the closed state to a half-open state. Our date show that the distances of the diagonal subunits increase from 41.0 Å at closed state to 45.7Å or 46.4 Å at a half-open state. It is the rotatory motion and flower-opening like motion of the gating rings which are thought to pull the bundle crossing gate to open ultimately. Compared with the 'Ca2+ bowl' at RCK2, the RCK1 Ca2+ sites make more contribution to opening the channel. The allosteric motions of the gating ring are regulated by three group of interactions. The first weakened group is thought to stabilize the close state; the second strengthened group is thought to stabilize the open state; the third group thought to lead AC region forming the CTD pore to coordinated motion, which exquisitely regulates the conformational changes during the opening of BK channels by Ca2+.

Polymorphisms and haplotypes of the TGF-ß1 gene are associated with risk of polycystic ovary syndrome in Chinese Han women.

OBJECTIVES: Transforming growth factor-beta 1 (TGF-ß1) is one of the multifunctional cytokine families. It takes part in a series of physiological and pathological processes in the human body, including wound healing, tissue fibrosis and embryonic development. Recent studies have shown that TGF-ß1 participates in the development of polycystic ovary syndrome (PCOS). This study was therefore designed to investigate the association of TGF-ß1 polymorphism with the risk of PCOS. STUDY DESIGN: We enrolled 328 PCOS patients and 358 healthy individuals in this study. Five single nucleotide polymorphisms (SNPs) - rs4803457C/T, rs11466313 deletion/AGG, rs2217130C/T, rs1800469C/T and rs1800470C/T - were detected using Snapshot technology. Linkage disequilibrium and haplotype analysis was conducted among the five SNPs. The relationship between genotypes and haplotypes and the risk of PCOS was also explored. RESULTS: The TT/CT/CC genotype frequencies of rs4803457 in the PCOS group and the control group were 0.2805/0.4878/0.2317 and 0.3659/0.4749/0.1592 respectively. The C/T allele frequencies in the PCOS group and control group were 0.3813/0.6187 and 0.3966/0.6034 respectively. There were significant differences in genotype distribution frequencies and allele frequencies between these two groups (P=0.018). Logistic regression analysis showed that CC genotype had higher risk of PCOS than the no CC genotype in rs4803457 loci (OR=1.75, 95%CI=1.11-2.75). Haplotype analysis further showed that the haplotypes "T-del-C-C-C", "C-del-C-C-C" and "C-del-C-T-C" were associated with the highest risk of PCOS. However, for rs11466313 deletion/AGG, rs2217130C/T, rs1800469C/T and rs1800470C/T, no significant association with PCOS risk was observed. CONCLUSION: The TGF-ß1 gene rs4803457C/T polymorphism is associated with susceptibility to PCOS, and is the key contributor for the development of PCOS in Chinese Han women. The haplotypes T-del-C-C-C, C-del-C-C-C and C-del-C-T-C are also risk factors for PCOS susceptibility among Chinese Han women.

MiR-133b regulates the expression of the Actin protein TAGLN2 during oocyte growth and maturation: a potential target for infertility therapy.

Infertility is an area of increasing in life science research. Although follicular maturation disorders and anovulation are the primary causations of infertility, its molecular mechanism is not well understood. Recent research has shown that microRNAs (miRNAs) might play an important role in the regulation of ovarian follicle development and maturation. In this study, the expression of miRNAs in metaphase I (MI) oocytes treated with or without insulin-like growth factor 1 (IGF-1) was observed by microRNA microarray analysis. Results show that 145 miRNAs were up-regulated and 200 miRNAs were down-regulated in MI oocytes after IGF-1 treatment. MiR-133b, which was up-regulated more than 30-fold, was chosen for further research. As a potential target of miR133b, transgelin 2 (TAGLN2) gene was down-regulated, at both transcription and translation levels, in miR-133b- over-expressed 293T cells, but TAGLN2 was up-regulated when the expression of miR-133b was inhibited. Furthermore, the expression level of TAGLN2 in the ovaries of 8-week- old mice was higher than that observed in 4-week-old mice. Immunofluorescence experiments showed that TAGLN2 was located in the cytoplasm. In general, our results indicate that miR-133b may play important roles in the growth and maturation of oocytes by regulating its potential target, TAGLN2, at both transcription and translation levels. Therefore, our research provides a potential new target for infertility therapy.