Articles by Askar M. Akimzhanov in JoVE
Monitoring dynamische veranderingen in het mitochondriaal calciumgehalte Tijdens Apoptosis Met behulp van een genetisch gecodeerd Calcium Sensor Askar M. Akimzhanov1, Darren Boehning1 1Department of Neuroscience and Cell Biology, University of Texas Medical Branch Dit protocol beschrijft een methode voor real-time meting van mitochondriale calcium fluxen door fluorescerende beeldvorming. De methode maakt gebruik van een circulair gepermuteerd YFP-gebaseerde dual-excitatie ratiometrische calcium sensor (ratiometrische pericam-mt) selectief, uitgedrukt in mitochondriën.
Other articles by Askar M. Akimzhanov on PubMed
Chromatin Remodeling of Interleukin-17 (IL-17)-IL-17F Cytokine Gene Locus During Inflammatory Helper T Cell Differentiation The Journal of Biological Chemistry. Mar, 2007 | Pubmed ID: 17218320 During differentiation of naive CD4+ helper T (TH) cells into effector cells, specific cytokine gene loci undergo extensive changes in chromatin modification. A novel lineage of TH cells that is regulated by transforming growth factor-beta (TGFbeta) and interleukin-6 (IL-6) has been identified recently as promoting tissue inflammation. These inflammatory TH (THi) cells, also called TH17 or TH(IL-17), produce IL-17 and IL-17F, two highly homologous cytokines that have genes located in the same chromosomal region. Here, using chromatin immunoprecipitation techniques, we have demonstrated that similar to the regulation in TH1 and TH2 cell lineages, polarization of THi cells was accompanied by selective chromatin remodeling events. Histone H3 acetylation and Lys-4 tri-methylation were specifically associated with IL-17 and IL-17F gene promoters in THi lineage. At an early stage of T cell activation, histone acetylation on these promoters was greatly promoted by a combination of TGFbeta and IL-6, suggesting their synergistic role in initiating chromatin accessibility for transcription factors. Furthermore, we identified multiple noncoding sequences within the IL-17-IL-17F locus conserved across species. These elements were also associated with hyperacetylated histone 3 in a lineage-specific manner and may thus serve as potential regulatory regions. In summary, our results demonstrate for the first time that THi cell differentiation is associated with epigenetic changes in the IL-17-IL-17F locus, which suggests novel mechanisms in T cell functional regulation.
T-cell Receptor Complex is Essential for Fas Signal Transduction Proceedings of the National Academy of Sciences of the United States of America. Aug, 2010 | Pubmed ID: 20696918 The Fas receptor (also known as CD95 and APO-1) is a member of the tumor necrosis factor alpha-family of death receptors that mediate T-cell responses. Here, we show that Fas receptor signaling requires a functional T-cell receptor (TCR) complex. Fas receptor directly binds to and activates TCR components in a stimulus-dependent manner. Fas receptor stimulation does not activate canonical downstream TCR pathways, but instead the TCR complex is required specifically for Fas-mediated calcium release. Importantly, null mutations in Lck, ZAP70, and the TCR alpha- and beta-chains abrogate Fas signaling. Our results reveal a direct role for the TCR complex in mediating Fas-specific signaling events critical for T-cell homeostasis.