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Mechanisms Underlying the Protective Effect of the Peroxiredoxin-6 Are Mediated via the Protection of Astrocytes during Ischemia/Reoxygenation.
Int J Mol Sci
August 2021
A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia.
Ischemia-like conditions reflect almost the entire spectrum of events that occur during cerebral ischemia, including the induction of oxidative stress, Ca overload, glutamate excitotoxicity, and activation of necrosis and apoptosis in brain cells. Mechanisms for the protective effects of the antioxidant enzyme peroxiredoxin-6 (Prx-6) on hippocampal cells during oxygen-glucose deprivation/reoxygenation (OGD/R) were investigated. Using the methods of fluorescence microscopy, inhibitory analysis, vitality tests and PCR, it was shown that 24-h incubation of mixed hippocampal cell cultures with Prx-6 does not affect the generation of a reversible phase of a OGD-induced rise in Ca ions in cytosol ([Ca]), but inhibits a global increase in [Ca] in astrocytes completely and in neurons by 70%.
View Article and Find Full Text PDFCell cryopreservation is an essential tool for drug toxicity/function screening and transporting cell-based therapies, and is essential in most areas of biotechnology. There is a challenge, however, associated with the cryopreservation of cells in monolayer format (attached to tissue culture substrates) which gives far lower cell yields (<20% typically) compared to suspension freezing. Here we investigate the mechanisms by which the protective osmolyte l-proline enhances cell-monolayer cryopreservation.
View Article and Find Full Text PDFEffect of 3-Day and 21-Day Hypoxic Preconditioning on Recovery Following Cerebral Ischemia in Rats.
Adv Exp Med Biol
May 2021
Departments of Physiology & Biophysics, Case Western Reserve University, Cleveland, OH, USA.
We have previously reported that in a rat model of chronic hypoxia, HIF-1α and its target genes have significantly accumulated by 3 days of exposure, whereas no significant increase in capillary density has occurred; there is a significant increase in capillary density at 21 days of chronic hypoxic exposure. In this study we hypothesize that by utilizing 3 days and 21 days of hypoxic preconditioning, we would distinguish between the relative neuroprotective contributions of the accumulation of HIF-1α and its target genes and angiogenic adaptation in a rat middle cerebral artery occlusion (MCAO) model. Rats were randomly assigned to either hypoxic precondition groups (3-day and 21-day hypoxia) or normoxic control group.
View Article and Find Full Text PDFModeling Radiation-Induced Neoplastic Cell Transformation In Vitro and Tumor Induction In Vivo with the Local Effect Model.
Radiat Res
May 2021
GSI Helmholtz Centre for Heavy Ion Research, Department of Biophysics, Darmstadt, Germany.
Ionizing radiation induces DNA damage to cycling cells which, if left unrepaired or misrepaired, can cause cell inactivation or heritable, viable mutations. The latter can lead to cell transformation, which is thought to be an initial step of cancer formation. Consequently, the study of radiation-induced cell transformation promises to offer insights into the general properties of radiation carcinogenesis.
View Article and Find Full Text PDFCRAC channel opening is determined by a series of Orai1 gating checkpoints in the transmembrane and cytosolic regions.
J Biol Chem
August 2021
Institute of Biophysics, JKU Life Science Center, Johannes Kepler University Linz, Linz, Austria. Electronic address:
The initial activation step in the gating of ubiquitously expressed Orai1 calcium (Ca) ion channels represents the activation of the Ca-sensor protein STIM1 upon Ca store depletion of the endoplasmic reticulum. Previous studies using constitutively active Orai1 mutants gave rise to, but did not directly test, the hypothesis that STIM1-mediated Orai1 pore opening is accompanied by a global conformational change of all Orai transmembrane domain (TM) helices within the channel complex. We prove that a local conformational change spreads omnidirectionally within the Orai1 complex.
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