Susceptibility to ATP depletion of primary proximal tubular cell cultures derived from mice lacking either the alpha1 or the alpha2 isoform of the catalytic domain of AMPK.

International audienceBACKGROUND: The purpose of this study was to determine whether AMPK influences the survival of primary cultures of mouse proximal tubular (MPT) cells subjected to metabolic stress. Previous studies, using an immortalized MPT cell line, suggest that AMPK is activated during metabolic stress, and ameliorates stress-induced apoptosis of these cells. METHODS: Primary MPT cells were cultured from AMPK knockout (KO) mice lacking either the alpha1 or the alpha2 isoform of the catalytic domain of AMPK. MPT cells were subjected to ATP depletion using antimycin A. RESULTS: Surprisingly, there was no difference in the amount of death induced by metabolic stress of MPT cells from either type of AMPK KO mice compared to its WT control. Moreover, inhibition of the activity of the alpha1 isoform in primary MPT cells from alpha2-/- mice (pharmacologically, via compound C) or inhibition of the alpha2 isoform in primary MPT cells from alpha1-/- mice (molecularly, via knockdown) both decreased cell viability equivalently in response to metabolic stress. The explanation for this unexpected result appears to be an adaptive increase in expression of the non-deleted alphaisoform. As a consequence, total As a consequence-domain expression (i.e. alpha1 + alpha2), is comparable in kidney cortex and in cultured MPT cells derived from either type of KO mouse versus its WT control. Importantly, each alphaisoform appears able to compensate fully for the absence of the other, with respect to both the phosphorylation of downstream targets of AMPK and the amelioration of stress-induced cell death. CONCLUSIONS: These findings not only confirm the importance of AMPK as a pro-survival kinase in MPT cells during metabolic stress, but also show, for the first time, that each of the two alpha-isoforms can substitute for the other in MPT cells from AMPK KO mice with regard to amelioration of stress-induced loss of cell viability

Structure and stability of arsenate adsorbed on α-Al2O3 single-crystal surfaces investigated using grazing-incidence EXAFS measurement and DFT calculation

Direct characterization of contaminants on single-crystal planes is required because the specific adsorption characteristics on different exposed crystal planes constitute their actual behavior at water–mineral interfaces in aquifers. Here, the structure and stability of arsenate on α-Al2O3 (0001) and (View the MathML source112¯0) surfaces were characterized by using a combination of grazing-incidence extended X-ray absorption fine structure (GI-EXAFS) spectra and periodic density functional theory (DFT) calculation. The combined results indicated that arsenate was mainly adsorbed as inner-sphere monodentate and bidentate complexes on both surfaces, but the orientational polar angles on the (0001) surface were commonly 10–20° greater than that on the (View the MathML source112¯0) surface. The DFT calculation showed that the large polar angle was more favorable for arsenate stabilized on the alumina surfaces. Based on the spectroscopic and computational data, the dominant bonding modes of arsenate on the two crystal planes of α-Al2O3 were identified as bidentate binuclear structures, and the (0001) surface displayed a stronger affinity toward arsenate

Highly efficient and irreversible removal of cadmium through the formation of a solid solution

Sulfur-containing materials are very attractive for the efficient decontamination of some heavy metals. However, the effective and irreversible removal of Cd2+, coupled with a high uptake efficiency, remains a great challenge due to the relatively low bond dissociation energy of CdS. Herein, we propose a new strategy to overcome this challenge, by the incorporation of Cd2+ into a stable ZnxCd1-xS solid solution, rather than into CdS. This can be realised through the adsorption of Cd2+ by ZnS nanoparticles, which have exhibited a Cd2+ uptake capacity of approximate 400 mg g−1. Through this adsorption mechanism, the Cd2+ concentration in a contaminated solution could effectively be reduced from 50 ppb to 80% uptake capacity for Cd2+, compared with only 9% uptake capacity for similarly-aged FeS particles. This work reveals a new mechanism for Cd2+ removal with ZnS and establishes a valuable starting point for further studies into the formation of solid solutions for hazardous heavy metal removal applications

Collective total synthesis of stereoisomeric yohimbine alkaloids

Abstract Stereoisomeric polycyclic natural products are important for drug discovery-based screening campaigns, due to the close correlation of stereochemistry with diversified bioactivities. Nature generates the stereoisomeric yohimbine alkaloids using bioavailable monoterpene secolaganin as the ten-carbon building block. In this work, we reset the stage by the development of a bioinspired coupling, in which the rapid construction of the entire pentacyclic skeleton and the complete control of all five stereogenic centers are achieved through enantioselective kinetic resolution of an achiral, easily accessible synthetic surrogate. The stereochemical diversification from a common intermediate allows for the divergent and collective synthesis of all four stereoisomeric subfamilies of yohimbine alkaloids through orchestrated tackling of thermodynamic and kinetic preference