Background— Prolonged atrial fibrillation (AF) results in electrical, structural, and gap-junctional remodeling. We examined the reversibility of the changes in (ultra)structure and gap junctions. Methods and Results— Four groups of goats were used: (1) sinus rhythm (SR), (2) 4 months’ AF (4 mo AF), (3) 2 months’ SR after 4 mo AF (2 mo post-AF), and (4) 4 months’ SR after 4 mo AF (4 mo post-AF). Atria were characterized electrophysiologically, (ultra)structure was studied by light and electron microscopy, and structural and gap-junctional protein expression was studied by immunohistochemistry or Western blotting. The atrial effective refractory period had completely returned to normal values 2 mo post-AF. Induced AF episodes still lasted for minutes at 2 and 4 mo post-AF, compared with seconds in the SR group. Structural abnormalities were still present at 2 and 4 mo post-AF, although to a lesser extent. The increased atrial myocyte diameter was back to normal at 4 mo post-AF. The number of myocytes with severe myolysis had almost normalized 4 mo post-AF, whereas myocytes with mild myolysis remained significantly increased. Extracellular matrix area fraction after 4 mo AF was similar to SR. However, the extracellular matrix fraction per myocyte had increased after 4 mo AF and remained higher post-AF. Changes in expression of structural proteins were partially restored post-AF. The reduction of connexin 40 that was observed during AF was completely reversed at 4 mo post-AF. Conclusions— Recovery from structural remodeling after 4 mo AF is a slow process and is still incomplete 4 mo post-AF. Several months post-AF, the duration of AF episodes is still prolonged (minutes).
The time course of changes in the distribution and content of Cx40 gap junctions as observed during endocardial burst pacing of the goat atrium suggests that Cx40 gap junctional remodeling might be involved in the pathogenesis of sustained atrial fibrillation.
Progression through mitosis requires the inactivation of the protein kinase activity of the p34dC2-cyclin complex by a mechanism involving the degradation of cycling. We have examined the stability in Xenopus egg extracts of radiolabeled Xenopus or sea urchin B-type cyclins synthesized in reticulocyte lysates. Xenopus cyclin B2 and sea urchin cyclin B were stable in metaphase extracts from unfertilized eggs but were specifically degraded following addition of Ca2+ to the extracts. The degradation of either cyclin was inhibited by the addition of an excess of unlabeled Xenopus cyclin B2 but not by the addition of a number of control proteins.A truncated protein containing only the amino terminus ofXenopus cyclin B2, including sequences known to be essential for cyclin degradation in other species, also inhibited cyclin degradation, even though the truncated protein was stable in extracts following Ca2' addition. The addition of the truncated protein did not stimulate histone H1 kinase activity in extracts but prevented the loss of H1 kinase activity that normally follows Ca2+ addition to metaphase extracts. When the amino-terminal fragment was added to extracts capable of several cell cycles in vitro, progression through the first mitosis was inhibited and elevated histone H1 kinase activity was maintained. These results indicate that although the amino terminus of cyclin does not contain all of the information necessary for cyclin destruction, it is capable of interacting with components of the cyclin destruction pathway and thereby preventing the degradation of full-length cyclins.Various approaches to study the regulation of the entry into mitosis in eukaryotic cells have converged to identify a complex that contains p34, a 34-kDa serine-threonine protein kinase first identified as the product of the cell division cycle gene cdc2 or CDC28 in the yeasts Schizosaccharomycespombe and Saccharomyces cerevisiae, and a cyclin as an essential component in cell cycle control (for reviews, see references 23, 38, and 41). The complex, when active as a protein kinase, is capable of causing nuclear envelope disassembly, chromosome condensation, and spindle formation, both when injected into immature oocytes and when added to cell extracts containing interphase nuclei. Formation of the complex is essential for generation of the protein kinase activity of p34, although other posttranslational controls, such as the phosphorylation and dephosphorylation of specific amino acids on p34, are also required (3,12,13,20,48).One level at which the activation of the p34-cyclin complex is regulated is by the availability of the cyclin subunits. Although the levels of p34 remain relatively constant in proliferating cells, cyclin levels vary dramatically with the cell cycle (for reviews, see references 17 and 35). Recently, members of the cyclin family that reach highest levels in late G1 phase and are likely to be involved in the control of S phase have been identified (for examples, see references 22, 31, and 51; for a review, see refe...
We have investigated the attachment of DNA to the nuclear matrix and chromosomal scaffold in synchronized bovine liver celfs. Label incorporated at the onset of the S phase remained preferentially associated with the matrix during the subsequent Gr phase and with a residual protein structure from dehistonized chromosomes during mitosis. On the other hand label incorporated during mid or late S phase was about equally distributed over the DNA molecule after a chase into the Gr phase. These results suggest that DNA is attached to the nuclear matrix and chromosome scaffolds by the origins of replication.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.