Affordable Access

deepdyve-link
Publisher Website

Astrocytes synthesize primary and cyclopentenone prostaglandins that are negative regulators of their proliferation.

Authors
  • Chistyakov, Dmitry V1
  • Grabeklis, Sevil2
  • Goriainov, Sergei V3
  • Chistyakov, Viktor V3
  • Sergeeva, Marina G2
  • Reiser, Georg4
  • 1 A.N. Belozersky Institute of Physico-Chemical-Biology, Moscow State-University, Moscow, Russia; Pirogov Russian National Research Medical University, Moscow, Russia.
  • 2 A.N. Belozersky Institute of Physico-Chemical-Biology, Moscow State-University, Moscow, Russia.
  • 3 Peoples' Friendship University of Russia (RUDN University), Moscow, Russia.
  • 4 Otto-von-Guericke-Universität Magdeburg, Medizinische Fakultät, Institut für Inflammation und Neurodegeneration (Neurobiochemie), Leipziger Straße 44, 39120, Magdeburg, Germany. Electronic address: [email protected] , (Germany)
Type
Published Article
Journal
Biochemical and Biophysical Research Communications
Publisher
Elsevier
Publication Date
Jun 02, 2018
Volume
500
Issue
2
Pages
204–210
Identifiers
DOI: 10.1016/j.bbrc.2018.04.040
PMID: 29634926
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Recently, the modulation of cellular inflammatory responses via endogenous regulators became a major focus of medically relevant investigations. Prostaglandins (PGs) are attractive regulatory molecules, but their synthesis and mechanisms of action in brain cells are still unclear. Astrocytes are involved in manifestation of neuropathology and their proliferation is an important part of astrogliosis, a cellular neuroinflammatory response. The aims of our study were to measure synthesis of PGs by astrocytes, and evaluate their influence on proliferation in combination with addition of inflammatory pathway inhibitors. With UPLC-MS/MS analysis we detected primary PGs (1410 ± 36 pg/mg PGE2, 344 ± 24 PGD2) and cyclopentenone PGs (cyPGs) (87 ± 17 15d-PGJ2, 308 ± 23 PGA2) in the extracellular medium after 24-h lipopolysaccharide (LPS) stimulation of astrocytes. PGs reduced astrocytic proliferation with the following order of potencies (measured as inhibition at 20 μM): most potent 15d-PGJ2 (90%) and PGA2 (80%), > PGD2 (40%) > 15d-PGA2 (20%) > PGE2 (5%), the least potent. However, PGF2α and 2-cyclopenten-1-one, and ciglitazone and rosiglitazone (synthetic agonists of PPARγ) had no effect. Combinations of cyPGs with SC-560 or NS-398 (specific anti-inflammatory inhibitors of cyclooxygenase-1 and -2, respectively) were not effective; while GW9662 (PPARγ antagonist) or MK-741 (inhibitor of multidrug resistance protein-1, MRP1, and CysLT1 receptors) amplified the inhibitory effect of PGA2 and 15d-PGJ2. Although concentrations of individual PGs and cyPGs are low, all of them, as well as primary PGs suppress proliferation. Thus, the effects are potentially additive, and activated PGs synthesis suppresses proliferation in astrocytes. Copyright © 2018 Elsevier Inc. All rights reserved.

Report this publication

Statistics

Seen <100 times