ARP3 promotes tumor metastasis and predicts a poor prognosis in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide. Therefore, the study of the precise molecular mechanism underlying hepatocarcinogenesis has profound significance. In this study, we found that the expression of ARP3 was significantly up-regulated in HCC tissues and cell lines. Studies in liver cancer specimens showed that the expression of ARP3 is closely related to the pathological grade, distant metastasis and vascular invasion of HCC. According to the results of multivariate analysis, ARP3 is an independent prognostic factor for HCC patients. In vitro, knockdown of ARP3 expression significantly inhibited the invasion and migration of HCC cells and altered the expression of EMT markers. Based on the above conclusions, we conclude that ARP3 may be a potential prognostic indicator and therapeutic target for HCC patients.

Perfluorooctanesulfonate (PFOS)-induced Sertoli cell injury through a disruption of F-actin and microtubule organization is mediated by Akt1/2.

PFOS (perfluorooctanesulfonate, or perfluorooctane sulfonic acid) is an anthropogenic fluorosurfactant widely used in consumer products. While its use in Europe, Canada and the U.S. has been banned due to its human toxicity, it continues to be used in China and other developing countries as a global pollutant. Herein, using an in vitro model of Sertoli cell blood-testis barrier (BTB), PFOS was found to induce Sertoli cell injury by perturbing actin cytoskeleton through changes in the spatial expression of actin regulatory proteins. Specifically, PFOS caused mis-localization of Arp3 (actin-related protein 3, a branched actin polymerization protein) and palladin (an actin bundling protein). These disruptive changes thus led to a dis-organization of F-actin across Sertoli cell cytosol, causing truncation of actin microfilament, thereby failing to support the Sertoli cell morphology and adhesion protein complexes (e.g., occludin-ZO-1, CAR-ZO-1, and N-cadherin-ß-catenin), through a down-regulation of p-Akt1-S473 and p-Akt2-S474. The use of SC79, an Akt1/2 activator [corrected], was found to block the PFOS-induced Sertoli cell injury by rescuing the PFOS-induced F-actin dis-organization. These findings thus illustrate PFOS exerts its disruptive effects on Sertoli cell function downstream through Akt1/2. As such, PFOS-induced male reproductive dysfunction can possibly be managed through an intervention on Akt1/2 expression.

[Effect of low dose radiation on human [corrected] bone marrow mesenchymal stem cells by using proteomic analysis].

This study was aimed to investigate the effect of low dose radiation (LDR) on human bone marrow mesenchymal stem cells (MSCs) by using proteomic analysis. The bidirectional gel electrophoresis was used to establish the two-dimensional gel electrophoresis patterns of proteome in group of MSCs exposed to LDR and in group of sham irradiated MSCs, the matrix assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS) was used to identify the differentially expressed proteins in two groups. The results showed that among the differentially expressed proteins in the two groups, the expressions of 12 proteins were up-regulated, the expressions of 12 protein were down-regulated, 3 proteins disappeared after LDR, 12 proteins had been identified by MALDI-TOF-MS. In conclusion, the identified 12 proteins, such as prolyl 4-hydroxylase, dihydropyrimidinase-like 2 variant, ARP3 (actin-related protein 3, yeast) homolog, guanine nucleotide binding protein (G protein), phosphoglycerate mutase 1 may be related to mechanism of LDR effect. The study provides some new explanation for the mechanism of low dose radiation injury.

Profilin and actin-related proteins regulate microfilament dynamics during early mammalian embryogenesis.

BACKGROUND: Profilins are ubiquitous proteins widely distributed in animals, including humans. They regulate actin polymerization by sequestering actin monomers in association with other actin-related proteins (Arps). Actin remodelling is essential for oocyte maturation, fertilization and embryo development; yet the role of profilins in these events is not well understood. Here we investigate profilin distribution and function during bovine fertilization and early embryogenesis, and we examine profilin localization with respect to the co-distribution of other Arps. METHODS AND RESULTS: Western blotting, confocal microscopy with immunofluorescence and protein inhibition studies with antibodies were implemented. Profilin distributes inside interphase nuclei, throughout the cytoplasm and near the cell cortex at different stages of bovine oocyte maturation, fertilization and embryo development. Expression is detected through the blastocyst stage, where profilin localizes to the inner cell mass as well as trophectoderm. Profilin co-distributes with actin monomers and Arps vasodilator-stimulated phospho protein, p140mDia, Arp 3 and p80 coilin in pronucleate-stage zygotes. Antiprofilin antibodies inhibit normal embryo development by disrupting microfilaments, but not microtubules, and result in a higher concentration of profilin and p140mDia mislocalized to the cortex. CONCLUSIONS: These findings demonstrate that profilin regulates actin dynamics both within the cytoplasm and inside the nuclei of developing mammalian embryos and that its function is essential during fertilization to ensure successful development.