34 research outputs found
ΠΠ΅ΠΎΡ ΠΈΠΌΠΈΡΠ΅ΡΠΊΠ°Ρ ΡΠΏΠ΅ΡΠΈΡΠΈΠΊΠ° ΠΎΠ·Π΅ΡΠ½ΡΡ Π²ΠΎΠ΄ ΠΊΡΠ»ΡΠ½Π΄ΠΈΠ½ΡΠΊΠΎΠΉ ΡΡΠ΅ΠΏΠΈ ΠΠ»ΡΠ°ΠΉΡΠΊΠΎΠ³ΠΎ ΠΊΡΠ°Ρ
ΠΠ·ΡΡΠ΅Π½Π° Π³Π΅ΠΎΡ
ΠΈΠΌΠΈΡΠ΅ΡΠΊΠ°Ρ ΡΠΏΠ΅ΡΠΈΡΠΈΠΊΠ° ΠΎΠ·Π΅ΡΠ½ΡΡ
Π²ΠΎΠ΄ ΡΠ΅ΡΡΠΈΡΠΎΡΠΈΠΈ ΠΡΠ»ΡΠ½Π΄ΠΈΠ½ΡΠΊΠΎΠΉ ΡΡΠ΅ΠΏΠΈ ΠΠ»ΡΠ°ΠΉΡΠΊΠΎΠ³ΠΎ ΠΊΡΠ°Ρ. Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ ΠΏΠΎΠΊΠ°Π·Π°Π»ΠΈ, ΡΡΠΎ Π½Π° ΡΠ΅ΡΡΠΈΡΠΎΡΠΈΠΈ ΡΠ°Π·Π²ΠΈΡΡ Π² ΠΎΡΠ½ΠΎΠ²Π½ΠΎΠΌ Ρ
Π»ΠΎΡΠΈΠ΄Π½ΡΠ΅ ΠΈ ΡΠ΅ΠΆΠ΅ ΡΠΎΠ΄ΠΎΠ²ΡΠ΅ ΠΎΠ·Π΅ΡΠ° Ρ Π½Π°ΡΡΠΈΠ΅Π²ΡΠΌ ΡΠΎΡΡΠ°Π²ΠΎΠΌ. ΠΡΠ΅Π΄ΡΡΠ°Π²Π»Π΅Π½ΠΎ, ΡΡΠΎ Π½Π° Π½Π°ΠΊΠΎΠΏΠ»Π΅Π½ΠΈΠ΅ ΡΠ»Π΅ΠΌΠ΅Π½ΡΠΎΠ² Π² ΡΠ°ΡΡΠ²ΠΎΡΠ΅ Π½Π°ΠΈΠ±ΠΎΠ»ΡΡΠ΅Π΅ Π²Π»ΠΈΡΠ½ΠΈΠ΅ ΠΎΠΊΠ°Π·ΡΠ²Π°ΡΡ ΠΈΡΠΏΠ°ΡΠ΅Π½ΠΈΠ΅, Π²ΡΠΎΡΠΈΡΠ½ΠΎΠ΅ ΠΌΠΈΠ½Π΅ΡΠ°Π»ΠΎΠΎΠ±ΡΠ°Π·ΠΎΠ²Π°Π½ΠΈΠ΅ ΠΈ ΡΠ°Π·Π»ΠΈΡΠ½ΡΠ΅ Π±ΠΈΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΏΡΠΎΡΠ΅ΡΡΡ. The geochemical specifics of lake water in Kulunda steppe area (Altai Krai, Russia) is described. The results showed mainly chloride and less soda lakes with a sodium compound are located there. It presented that the accumulation of elements in saline solution have the greatest impact of secondary minerals' formation and various biological processes
Integrated Proteomics Unveils Nuclear PDE3A2 as a Regulator of Cardiac Myocyte Hypertrophy
Background: Signaling by cAMP is organized in multiple distinct subcellular nanodomains regulated by cAMP-hydrolyzing PDEs (phosphodiesterases). Cardiac Ξ²-adrenergic signaling has served as the prototypical system to elucidate cAMP compartmentalization. Although studies in cardiac myocytes have provided an understanding of the location and properties of a handful of cAMP subcellular compartments, an overall view of the cellular landscape of cAMP nanodomains is missing. Methods: Here, we combined an integrated phosphoproteomics approach that takes advantage of the unique role that individual PDEs play in the control of local cAMP, with network analysis to identify previously unrecognized cAMP nanodomains associated with Ξ²-adrenergic stimulation. We then validated the composition and function of one of these nanodomains using biochemical, pharmacological, and genetic approaches and cardiac myocytes from both rodents and humans. Results: We demonstrate the validity of the integrated phosphoproteomic strategy to pinpoint the location and provide critical cues to determine the function of previously unknown cAMP nanodomains. We characterize in detail one such compartment and demonstrate that the PDE3A2 isoform operates in a nuclear nanodomain that involves SMAD4 (SMAD family member 4) and HDAC-1 (histone deacetylase 1). Inhibition of PDE3 results in increased HDAC-1 phosphorylation, leading to inhibition of its deacetylase activity, derepression of gene transcription, and cardiac myocyte hypertrophic growth. Conclusions: We developed a strategy for detailed mapping of subcellular PDE-specific cAMP nanodomains. Our findings reveal a mechanism that explains the negative long-term clinical outcome observed in patients with heart failure treated with PDE3 inhibitors