RacGAP1 ameliorates acute kidney injury by promoting proliferation and suppressing apoptosis of renal tubular cells
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Authors: Zhou, Weiran; Zhao, Shuan; Xu, Sujuan; Sun, Zhaoxing; Liang, Yiran; Ding, Xiaoqiang
Abstract
Background: Acute kidney injury (AKI) remains correlated with high mortality. Novel therapeutic strategies are urgently needed for AKI patients. Rac GTPase-activating protein 1 (RacGAP1) regulates the activity of RhoGTPase and acts as a predictive biomarker in several types of malignant tumor but the role of RacGAP1 in AKI has not been revealed. Methods: Animal models of AKI induced by renal ischemia-reperfusion (I/R) and cisplatin treatment were generated in C57BL/6 mice. Hypoxia/reoxygenation (H/R) and cisplatin treatment were practiced in human renal tubular epithelial (HK-2) and renal tubular duct epithelial cells of rat (NRK-52E) cells. The role of RacGAP1 in cell proliferation and apoptosis was estimated using western bolting, immunocytochemistry and flow cytometry. Verteporfin was used to activate the Hippo pathway to show whether the protective effects of RacGAP1 on cell growth and survival in renal tubular cells were dependent on the activation of YAP. Results: The expression of RacGAP1 was significantly increased in mice kidneys after I/R or cisplatin treatment, combined with increased expression of RacGAP1 in H/R or cisplatin challenged cells. Overexpression of RacGAP1 protected HK2 and NRK-52E cells by promoting proliferation and decreasing apoptosis. We also disclosed that RacGAP1 exerted its function through activation of YAP. Conclusion: The present study provides evidence that RacGAP1 is involved in AKI. It promotes proliferation and limits apoptosis of tubular epithelial cells via stimulating activation and nuclear translocation of YAP. Consequently, RacGAP1 may be a novel therapeutic target for AKI. (C) 2020 Elsevier Inc. All rights reserved.
Low-temperature and purification-free stereocontrolled ring-opening polymerisation of lactide in supercritical carbon dioxide
GREEN CHEMISTRY
Authors: Bassett, Simon P.; Russell, Andrew D.; McKeown, Paul; Robinson, Isabel; Forder, Thomas R.; Taresco, Vincenzo; Davidson, Matthew G.; Howdle, Steven M.
Abstract
A stereoselective, solvent-free ring-opening polymerisation (ROP) of lactide (LA) in supercritical carbon dioxide (scCO(2)) is reported for the first time. The key aim is to exploit scCO(2) to lower the temperature of traditional melt polymerisations, lowering the energy requirement and leading to cleaner polymeric materials. We have utilised a zirconium amine-trisphenolate initiator-stereoselective catalyst [((PrO)-Pr-i)Zr(OPh(Bu-t)(2)-CH2)(3)N] to yield highly heterotactic poly(lactide) (PLA) homopolymer (P-r = 0.74-0.84) from rac-LA, demonstrating control of the PLA microstructure in scCO(2). In addition, high monomer conversion (86-93%) was achieved in short reaction time (1 h), affording poly(lactide) with a very low degree of transesterification and narrow molecular weight distribution. Most importantly, all the reactions were performed at only 80 degrees C, almost 100 degrees C lower than the conventional melt process (typically performed at 130-180 degrees C), representing a very significant potential energy saving.
COA
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