Cytosolic phospholipase A2 regulates lipid homeostasis under osmotic stress through PPARγ.
| Title: | Cytosolic phospholipase A |
|---|---|
| Authors: | Parra, Leandro Gastón1,2 (AUTHOR) lparra@docente.ffyb.uba.ar, Erjavec, Luciana Cecilia1,2 (AUTHOR), Casali, Cecilia Irene1,2 (AUTHOR) ccasali@ffyb.uba.ar, Zerpa Velazquez, Andrea1 (AUTHOR), Weber, Karen1 (AUTHOR), Setton‐Avruj, Clara Patricia2,3 (AUTHOR) setton@qb.ffyb.uba.ar, Fernández Tome, María del Carmen1,2 (AUTHOR) fertome@ffyb.uba.ar |
| Source: | FEBS Journal. Feb2024, Vol. 291 Issue 4, p722-743. 22p. |
| Subject Terms: | *PHOSPHOLIPASES, *ARACHIDONIC acid, *PHOSPHOLIPASE A2, *PEROXISOME proliferator-activated receptors, *HOMEOSTASIS, *CELL survival, *LIPID metabolism |
| Abstract: | Physiologically, renal medullary cells are surrounded by a hyperosmolar interstitium. However, different pathological situations can induce abrupt changes in environmental osmolality, causing cell stress. Therefore, renal cells must adapt to survive in this new condition. We previously demonstrated that, among the mechanisms involved in osmoprotection, renal cells upregulate triglyceride biosynthesis (which helps preserve glycerophospholipid synthesis and membrane homeostasis) and cyclooxygenase‐2 (which generates prostaglandins from arachidonic acid) to maintain lipid metabolism in renal tissue. Herein, we evaluated whether hyperosmolality modulates phospholipase A2 (PLA2) activity, leading to arachidonic acid release from membrane glycerophospholipid, and investigated its possible role in hyperosmolality‐induced triglyceride synthesis and accumulation. We found that hyperosmolality induced PLA2 expression and activity in Madin‐Darby canine kidney cells. Cytosolic PLA2 (cPLA2) inhibition, but not secreted or calcium‐independent PLA2 (sPLA2 or iPLA2, respectively), prevented triglyceride synthesis and reduced cell survival. Inhibition of prostaglandin synthesis with indomethacin not only failed to prevent hyperosmolality‐induced triglyceride synthesis but also exacerbated it. Similar results were observed with the peroxisomal proliferator activated receptor gamma (PPARγ) agonist rosiglitazone. Furthermore, hyperosmolality increased free intracellular arachidonic acid levels, which were even higher when prostaglandin synthesis was inhibited by indomethacin. Blocking PPARγ with GW‐9662 prevented the effects of both indomethacin and rosiglitazone on triglyceride synthesis and even reduced hyperosmolality‐induced triglyceride synthesis, suggesting that arachidonic acid may stimulate triglyceride synthesis through PPARγ activation. These results highlight the role of cPLA2 in osmoprotection, since it is essential to provide arachidonic acid, which is involved in PPARγ‐regulated triglyceride synthesis, thus guaranteeing cell survival. [ABSTRACT FROM AUTHOR] |
| Copyright of FEBS Journal is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Academic Search Complete |
| Full text is not displayed to guests. | Login for full access. |
Be the first to leave a comment!