title: Angiotensin II activates different calcium signaling pathways in adipocytes.
abstract: Angiotensin II (Ang II) is an important mammalian neurohormone involved in reninangiotensin system. Ang II is produced both constitutively and locally by RAS systems, including white fat adipocytes. The influence of Ang II on adipocytes is complex, affecting different systems of signal transduction from early Са(2+) responses to cell proliferation and differentiation, triglyceride accumulation, expression of adipokine-encoding genes and adipokine secretion. It is known that white fat adipocytes express all RAS components and Ang II receptors (АТ1 and АТ2). The current work was carried out with the primary white adipocytes culture, and Са(2+) signaling pathways activated by Ang II were investigated using fluorescent microscopy. Са(2+)-oscillations and transient responses of differentiated adipocytes to Ang II were registered in cells with both small and multiple lipid inclusions. Using inhibitory analysis and selective antagonists, we now show that Ang II initiates periodic Са(2+)-oscillations and transient responses by activating АТ1 and АТ2 receptors and involving branched signaling cascades: 1) Ang II → Gq → PLC → IP3 → IP3Rs → Ca(2+) 2) Gβγ → PI3Kγ → PKB 3) PKB → eNOS → NO → PKG 4) CD38 → cADPR → RyRs → Ca(2+) In these cascades, AT1 receptors play the leading role. The results of the present work open a perspective of using Ang II for correction of signal resistance of adipocytes often observed during obesity and type 2 diabetes.
authors: Laboratory of Intracellular Signalling, Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, Russia.
authors: Lyudmila P
authors: LP
authors: Dolgacheva
authors: Laboratory of Intracellular Signalling, Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, Russia.
authors: Maria V
authors: MV
authors: Turovskaya
authors: Laboratory of Intracellular Signalling, Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, Russia; Laboratory of System Biochemistry, Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, Russia.
authors: Vladimir V
authors: VV
authors: Dynnik
authors: Laboratory of Intracellular Signalling, Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, Russia.
authors: Valery P
authors: VP
authors: Zinchenko
authors: Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg, Russia.
authors: Nikolay V
authors: NV
authors: Goncharov
authors: Department of Biomedical Science, University of Sheffield, Sheffield S10 2TN, England, UK.
authors: Bazbek
authors: B
authors: Davletov
authors: Laboratory of Intracellular Signalling, Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, Russia. Electronic address: egorturovsky@gmail.com.
authors: Egor A
authors: EA
authors: Turovsky
mesh_terms: D052438:Adipocytes, White / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000804:Angiotensin II / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling; D002454:Cell Differentiation; D066292:Lipid Droplets / Q000648:ultrastructure; D051379:Mice; D061251:Primary Cell Culture; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism
chemical_list: D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II; D002118:Calcium
keywords: Adipocytes; Ang II receptors (AT(1) and AT(2)); Angiotensin II; Ca(2+) oscillations and transient responses; Calcium; Renin-angiotensin system