Mao-Xiang Zhu

Ionizing radiation causes serious injury to the human body and has long-time impacts on health. It is important to find optimal biomarkers for the early quick screening of exposed individuals. A series of miRNAs signatures have been developed as the new biomarkers for diagnosis, survival, and prognostic prediction of cancers. Here, we have identified the ionizing radiation-inducible miRNAs profile through microarray analysis. The biological functions were predicted for the top six upregulated miRNAs by 4 Gy γ-rays: miR-1246, miR-1307-3p, miR-3197, miR-4267, miR-5096 and miR-7641. The miRNA-gene network and target gene-pathway network analyses revealed that DNAH3 is the target gene associated with all the six miRNAs. GOLGB1 is related to 4 miRNAs and other 26 genes targeted by 3 miRNAs. The upregulation of fifteen miRNAs were further verified at 4 h and 24 h after 0 to 10 Gy irradiation in the human lymphoblastoid AHH-1 cells, and some demonstrated a dose-dependent increased. Six miRNAs, including miR-145, miR-663, miR-1273g-3p, miR-6090, miR-6727-5p and miR-7641, were validated to be dose-dependently upregulated at 4 h or 24 h post-irradiation in both AHH-1 and human peripheral blood lymphocytes irradiated ex vivo. This six-miRNA signature displays the superiority as a radiation biomarker for the translational application of screening and assessment of radiation exposed individuals.

Crotonaldehyde, a highly electrophilic α, β-unsaturated aldehyde, is a ubiquitous environmental pollutant and a risk factor for multiple respiratory diseases. Crotonaldehyde is highly volatile and hydrophilic, so it is efficiently absorbed in the respiratory tract. Alveolar macrophages are major effector cells of the nonspecific host defence in the lung. The aim of this study was to investigate the molecular mechanisms and signaling pathways responsible for cell death of alveolar macrophage induced by crotonaldehyde. Our results show that crotonaldehyde induces apoptosis in alveolar macrophages, as indicated by phosphatidylserine externalization and DNA fragmentation. Pretreatment of alveolar macrophages with N-acetylcysteine, ascorbic acid, α-tocopherol, superoxide dismutase inhibited crotonaldehyde-induced apoptosis. Crotonaldehyde-induced apoptosis was characterized by ROS generation, GSH depletion, loss of mitochondrial membrane potential (ΔΨm), the release of cytochrome c from mitochondria, caspase-3/7 and caspase-9 activation, elevation of intracellular Ca2+ concentration and the increase of p53 expression. Furthermore, pretreatment with either p53 inhibitor pifithrin-α or calcium chelator BAPTA-AM effectively attenuated apoptosis induced by crotonaldehyde. Taken together, our results showed that crotonaldehyde induce apoptosis in alveolar macrophages through intracellular calcium, mitochondria and p53 signaling pathways. These results would help to illustrate the mechanism of toxicity induced by crotonaldehyde and to look for a novel treatment for diseases induced by exposure to crotonaldehyde-rich pollutants such as cigarette smoke.