Centromere domain organization and histone modifications

Centromere function requires the proper coordination of several subfunctions, such as kinetochore assembly, sister chromatid cohesion, binding of kinetochore microtubules, orientation of sister kinetochores to opposite spindle poles, and their movement towards the spindle poles. Centromere structure appears to be organized in different, separable domains in order to accomplish these functions. Despite the conserved nature of centromere functions, the molecular genetic definition of the DNA sequences that form a centromere in the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe, in the fruit fly Drosophila melanogaster, and in humans has revealed little conservation at the level of centromere DNA sequences. Also at the protein level few centromere proteins are conserved in all of these four organisms and many are unique to the different organisms. The recent analysis of the centromere structure in the yeast S. pombe by electron microscopy and detailed immunofluorescence microscopy of Drosophila centromeres have brought to light striking similarities at the overall structural level between these centromeres and the human centromere. The structural organization of the centromere is generally multilayered with a heterochromatin domain and a central core/inner plate region, which harbors the outer plate structures of the kinetochore. It is becoming increasingly clear that the key factors for assembly and function of the centromere structure are the specialized histones and modified histones which are present in the centromeric heterochromatin and in the chromatin of the central core. Thus, despite the differences in the DNA sequences and the proteins that define a centromere, there is an overall structural similarity between centromeres in evolutionarily diverse eukaryotes.

Angiotensin-(1-7) improves the post-ischemic function in isolated perfused rat hearts

We evaluated the effects of angiotensin-(1-7) (Ang-(1-7)) on post-ischemic function in isolated hearts from adult male Wistar rats perfused according to the Langendorff technique. Local ischemia was induced by coronary ligation for 15 min. After ischemia, hearts were reperfused for 30 min. Addition of angiotensin II (Ang II) (0.20 nM, N = 10) or Ang-(1-7) (0.22 nM, N = 10) to the Krebs-Ringer perfusion solution (KRS) before the occlusion did not modify diastolic or systolic tension, heart rate or coronary flow (basal values for Ang-(1-7)-treated hearts: 0.72 ± 0.08 g, 10.50 ± 0.66 g, 216 ± 9 bpm, 5.78 ± 0.60 ml/min, respectively). During the period of occlusion, the coronary flow, heart rate and systolic tension decreased (values for Ang-(1-7)-treated hearts: 2.83 ± 0.24 ml/min, 186 ± 7 bpm, 6.95 ± 0.45 g, respectively). During reperfusion a further decrease in systolic tension was observed in control (4.95 ± 0.60 g) and Ang II-treated hearts (4.35 ± 0.62 g). However, in isolated hearts perfused with KRS containing Ang-(1-7) the further reduction of systolic tension during the reperfusion period was prevented (7.37 ± 0.68 g). The effect of Ang-(1-7) on the systolic tension was blocked by the selective Ang-(1-7) antagonist A-779 (2 nM, N = 9), by the bradykinin B2 antagonist HOE 140 (100 nM, N = 10), and by indomethacin pretreatment (5 mg/kg, ip, N = 8). Pretreatment with L-NAME (30 mg/kg, ip, N = 8) did not change the effect of Ang-(1-7) on systolic tension (6.85 ± 0.61 g). These results show that Ang-(1-7) at low concentration (0.22 nM) improves myocardial function (systolic tension) in ischemia/reperfusion through a receptor-mediated mechanism involving release of bradykinin and prostaglandins.

Neu vermehrte Post Charte der Chur Braunschweigischen und angrenzenden Lande

Kartta kuuluu A. E. Nordenskiöldin kokoelmaan