Down-regulation of the placental BCRP/ABCG2 transporter in response to hypoxia signaling

INTRODUCTION: The BCRP/ABCG2 efflux transporter protects the developing fetus by limiting the transplacental transfer of drugs and chemicals and prevents the apoptosis of trophoblasts. The purpose of this study was to determine whether hypoxia-related signaling alters placental BCRP expression and function in vitro and in human pregnancies. METHODS: Human BeWo choriocarcinoma cells were treated with the hypoxia mimetic, cobalt chloride (CoCl(2)), or 3% oxygen for 24-48 h. Activation of HIF-1α signaling and regulation of BCRP was assessed using qPCR, ELISA, western blotting and a fluorescent substrate transport assay. In addition, healthy term placentas from high altitude pregnancies with chronic hypoxia were assessed for BCRP expression. RESULTS: CoCl(2) and 3% oxygen increased HIF-1α protein signaling and decreased the mRNA and protein expression of BCRP by 30-75% in BeWo cells. Reduced BCRP expression corresponded with impaired efflux activity during hypoxia as evidenced by accumulation of the substrate Hoechst 33342. A number of transcription factors known to regulate BCRP, including AHR, NRF2 and PPARγ, were also coordinately down-regulated by 3% oxygen in BeWo cells. Moreover, women who gave birth at a high altitude (3100 m) exhibited signs of chronic placental hypoxia, including enhanced protein expression of the HIF-1α target GLUT1, and had reduced BCRP levels in microvillous membranes compared to women at a moderate altitude (1600 m). DISCUSSION: This study provides novel insight into the regulation of the placental BCRP transporter by hypoxia, which may be important for exposure of the fetus to chemicals during early development and in hypoxia-related pregnancy disorders

A review identifying the effectiveness of minimum quantity lubrication (MQL) during conventional machining

Government legislation and public opinion are the main drivers behind the movement of manufacturing companies towards sustainable production. Fundamentally, companies want to avoid future financial penalties and the industry is therefore under pressure to adapt new techniques and practices in order to become environmentally friendly. The cost efficiency of metal cutting operations is highly dependent on accuracy, excellent surface finish and minimized tool wear and, to this end, has traditionally made abundant use of cutting fluid in machining operations. However, these cutting fluids have been a major contributor to environmental and health issues. In recent years, an enormous effort to eradicate these adverse effects has been made with one important focus being the implementation of minimum quantity lubrication (MQL). In the present work, the authors have reviewed the current state of the art in MQL with a particular focus on drilling, turning, milling and grinding machining operations. Overall, it is concluded that MQL has huge potential as a substitute for conventional flood cooling