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p38 MAPK activation and STIM1-Orai3 association mediate TRPC6 externalization
Am J Physiol Cell Physiol. 2023 Apr 24. doi: 10.1152/ajpcell.00425.2022. Online ahead of print.ABSTRACTEndothelial cell (EC) migration is critical for the repair of monolayer disruption following angioplasties, but migration is inhibited by lipid oxidation products, including lysophosphatidylcholine (lysoPC), which open canonical transient receptor potential 6 (TRPC6) channels. TRPC6 activation requires an increase in intracellular Ca2+ concentration ([Ca2+]i), the source of which is unknown. LysoPC can activate phospholipase A2 to release arachidonic acid (ArA). ArA can activate arachidonic acid-regulated calcium (ARC) ch...
Source: American Journal of Physiology. Cell Physiology - April 24, 2023 Category: Cytology Authors: Pinaki Chaudhuri Priya Putta Michael A Rosenbaum Linda M Graham Source Type: research

UV ‐induced DNA Damage in Skin is Reduced by CaSR Inhibition
In this study we investigated whether the CaSR is involved more directly in protection from UV damage in studies of human keratinocytes in primary culture and in mouse skin studiedin vivo. siRNA-directed reductions in CaSR protein levels in human keratinocytes significantly reduced UV-induced direct cyclobutane pyrimidine dimers (CPD) by around 80% and oxidative DNA damage (8-OHdG) by around 65% compared to control transfected cells. Similarly, in untransfected cells, the CaSR negative modulator, NPS-2143 (500 nM), reduced UV-induced CPD and 8-OHdG by around 70%. NPS-2143 also enhanced DNA repair and reduced reactive oxyge...
Source: Photochemistry and Photobiology - March 15, 2022 Category: Science Authors: Chen Yang, Mark Stephen Rybchyn, Warusavithana Gunawardena Manori De Silva, Jim Matthews, Andrew J.A. Holland, Arthur David Conigrave, Rebecca Sara Mason Tags: RESEARCH ARTICLE Source Type: research

Creation of a new class of radiosensitizers for glioblastoma based on the mibefradil pharmacophore
We present in vivo pharmacokinetic studies of the top analogues with evidence of brain penetration. We also report a targeted siRNA-based screen which suggests a possible role for mTOR and Akt in DNA repair inhibition by this class of drugs. Taken together, these data reveal a new class of mibefradil-based DNA repair inhibitors which can be further advanced into pre-clinical testing and eventually clinical trials, as potential GBM radiosensitizers.PMID:33953843 | PMC:PMC8092340 | DOI:10.18632/oncotarget.27933
Source: Oncotarget - May 6, 2021 Category: Cancer & Oncology Authors: Sateja Paradkar James Herrington Adam Hendricson Piyasena Hewawasam Mark Plummer Denton Hoyer Ranjini K Sundaram Yulia V Surovtseva Ranjit S Bindra Source Type: research

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