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71.
The interactions between an oligomeric heat-shock protein, alpha-crystallin, and its individual subunits with unfolded proteins were monitored by surface plasmon resonance. Immobilization at the sensor chip allowed us for the first time to study isolated alpha-crystallin subunits under physiological conditions. We observe that these subunits, in contrast to alpha-crystallin oligomers, do not bind unfolded protein. Our data indicate that quaternary structure of alpha-crystallin is necessary for its chaperone-like activity. 相似文献
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73.
Involvement of mtDNA damage in free fatty acid-induced apoptosis 总被引:5,自引:0,他引:5
Grishko V Rachek L Musiyenko S Ledoux SP Wilson GL 《Free radical biology & medicine》2005,38(6):755-762
A growing body of evidence indicates that free fatty acids (FFA) can have deleterious effects on beta-cells. It has been suggested that the beta-cell dysfunction and death observed in diabetes may involve exaggerated activation of the inducible form of nitric oxide synthase (iNOS) by FFA, with the resultant generation of excess nitric oxide (NO). However, the cellular targets with which NO interact have not been fully identified. We hypothesized that one of these targets might be mitochondrial DNA (mtDNA). Therefore, experiments were initiated to evaluate damage to mtDNA caused by exposure of INS-1 cells to FFA (2/1 oleate/palmetate). The results showed that FFA caused a dose-dependent increase in mtDNA damage. Additionally, using ligation-mediated PCR, we were able to show that the DNA damage pattern at the nucleotide level was identical to the one induced by pure NO and different from damage caused by peroxynitrite or superoxide. Following exposure to FFA, apoptosis was detected by DAPI staining and cytochrome c release. Treatment of INS-1 cells with the iNOS inhibitor aminoguanidine protected these cells from mtDNA damage and diminished the appearance of apoptosis. These studies suggest that mtDNA may be a sensitive target for NO-induced toxicity which may provoke apoptosis in beta-cells following exposure to FFA. 相似文献
74.
Hyperspectral darkfield microscopy of PEGylated gold nanoparticles targeting CD44‐expressing cancer cells
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We present a new hyperspectral darkfield imaging system with a scanned broadband supercontinuum light source. We observed the specific attachment of the functionalized gold plasmonic nanoparticles (AuNPs) targeting CD44+ human breast cancer cells by conventional and by proposed hyperspectral darkfield microscopy. This wide‐field and low phototoxic hyperspectral imaging system has been successful for performing spectral three‐dimensional (3D) localization and spectroscopic identification of CD44‐targeted PEGylated AuNPs in fixed cell preparations. Such spatial and spectral information is essential for the improvement of nanoplasmonic‐based imaging, disease detection and treatment in complex biological environment. Presented system capability for 3D NP tracking will also enable investigation of specific sub‐cellular activity with the use of NPs as spectral sensors. (© 2013 WILEY‐VCH Verlag GmbH &Co. KGaA, Weinheim) 相似文献
75.
Plamena R. Angelova Minee L. Choi Alexey V. Berezhnov Mathew H. Horrocks Craig D. Hughes Suman De Margarida Rodrigues Ratsuda Yapom Daniel Little Karamjit S. Dolt Tilo Kunath Michael J. Devine Paul Gissen Mikhail S. Shchepinov Sergiy Sylantyev Evgeny V. Pavlov David Klenerman Andrey Y. Abramov Sonia Gandhi 《Cell death and differentiation》2021,28(5):1755
76.
Mitogen-activated protein kinases (MAPKs) are a family of proteins that constitute signaling pathways involved in processes that control gene expression, cell division, cell survival, apoptosis, metabolism, differentiation and motility. The MAPK pathways can be divided into conventional and atypical MAPK pathways. The first group converts a signal into a cellular response through a relay of three consecutive phosphorylation events exerted by MAPK kinase kinases, MAPK kinase, and MAPK. Atypical MAPK pathways are not organized into this three-tiered cascade. MAPK that belongs to both conventional and atypical MAPK pathways can phosphorylate both non-protein kinase substrates and other protein kinases. The latter are referred to as MAPK-activated protein kinases. This review focuses on one such MAPK-activated protein kinase, MAPK-activated protein kinase 5 (MK5) or p38-regulated/activated protein kinase (PRAK). This protein is highly conserved throughout the animal kingdom and seems to be the target of both conventional and atypical MAPK pathways. Recent findings on the regulation of the activity and subcellular localization, bona fide interaction partners and physiological roles of MK5/PRAK are discussed. 相似文献
77.
Tadashi Yoshida Sarah Galvez Sumit Tiwari Bashir M. Rezk Laura Semprun-Prieto Yusuke Higashi Sergiy Sukhanov Zipora Yablonka-Reuveni Patrice Delafontaine 《The Journal of biological chemistry》2013,288(33):23823-23832
Cachexia is a serious complication of many chronic diseases, such as congestive heart failure (CHF) and chronic kidney disease (CKD). Although patients with advanced CHF or CKD often have increased angiotensin II (Ang II) levels and cachexia and Ang II causes skeletal muscle wasting in rodents, the potential effects of Ang II on muscle regeneration are unknown. Muscle regeneration is highly dependent on the ability of a pool of muscle stem cells (satellite cells) to proliferate and to repair damaged myofibers or form new myofibers. Here we show that Ang II reduced skeletal muscle regeneration via inhibition of satellite cell (SC) proliferation. Ang II reduced the number of regenerating myofibers and decreased expression of SC proliferation/differentiation markers (MyoD, myogenin, and active-Notch) after cardiotoxin-induced muscle injury in vivo and in SCs cultured in vitro. Ang II depleted the basal pool of SCs, as detected in Myf5nLacZ/+ mice and by FACS sorting, and this effect was inhibited by Ang II AT1 receptor (AT1R) blockade and in AT1aR-null mice. AT1R was highly expressed in SCs, and Notch activation abrogated the AT1R-mediated antiproliferative effect of Ang II in cultured SCs. In mice that developed CHF postmyocardial infarction, there was skeletal muscle wasting and reduced SC numbers that were inhibited by AT1R blockade. Ang II inhibition of skeletal muscle regeneration via AT1 receptor-dependent suppression of SC Notch and MyoD signaling and proliferation is likely to play an important role in mechanisms leading to cachexia in chronic disease states such as CHF and CKD. 相似文献
78.
Torsten H. Walther Christina Gottselig Stephan L. Grage Moritz Wolf Attilio V. Vargiu Marco J. Klein Stefanie Vollmer Sebastian Prock Mareike Hartmann Sergiy Afonin Eva Stockwald Hartmut Heinzmann Olga V. Nolandt Wolfgang Wenzel Paolo Ruggerone Anne S. Ulrich 《Cell》2013,152(1-2):316-326
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79.
Mark P. Little Tamara V. Azizova Dimitry Bazyka Simon D. Bouffler Elisabeth Cardis Sergey Chekin Vadim V. Chumak Francis A. Cucinotta Florent de Vathaire Per Hall John D. Harrison Guido Hildebrandt Victor Ivanov Valeriy V. Kashcheev Sergiy V. Klymenko Olivier Laurent Kotaro Ozasa Soile Tapio Andrew M. Taylor Ioanna Tzoulaki Wendy L. Vandoolaeghe Richard Wakeford Lydia Zablotska Wei Zhang Steven E. Lipshultz 《Radiation and environmental biophysics》2013,52(1):157-159
80.
Kevin Hannigan Shridhar S. Kulkarni Volodymyr G. Bdzhola Andriy G. Golub Sergiy M. Yarmoluk Tanaji T. Talele 《Bioorganic & medicinal chemistry letters》2013,23(21):5790-5794
Poly(ADP-ribose)polymerase-1 (PARP-1) is an abundant and ubiquitous chromatin-bound nuclear protein. PARP-1, a DNA repair enzyme, has been in the limelight as a chemotherapeutic target. In this study, we demonstrated the successful use of structure-based virtual screening to identify inhibitors of PARP-1 from Otava databases comprised of nearly 260,000 compounds. Five novel inhibitors belonging to thienopyrimidinone, isoquinolinoquinazolinone, pyrroloquinazolinone, and cyclopentenothienopyrimidinone scaffolds revealed inhibitory potencies with IC50 values ranged from 9.57 μM to 0.72 μM. Structural features relevant to the activity of these novel compounds within the active site of PARP-1 are discussed in detail and will guide future SAR investigation on these scaffolds. 相似文献