Dorian Dolanc (Author), Tomaž Mark Zorec (Author), Zala Smole (Author), Anja Maver (Author), Anemari Horvat (Author), Thanigaimalai Pillaiyar (Author), Saša Trkov (Author), Nina Vardjan (Author), Marko Kreft (Author), Helena Chowdhury Haque (Author), Robert Zorec (Author)

Abstract

G-protein-coupled receptors (GPCRs) represent a family with over 800 members in humans, and one-third of these are targets for approved drugs. A large number of GPCRs have unknown physiologic roles. Here, we investigated GPR27, an orphan GPCR belonging to the family of super conserved receptor expressed in the brain, with unknown functions. Cytosolic levels of L-lactate ([lactate]i), the end product of aerobic glycolysis, were measured with the Laconic fluorescence resonance energy transfer nanosensor. In single 3T3 wild-type (WT) embryonic cells, the application of 8535 (1 µM), a surrogate agonist known to activate GPR27, resulted in an increase in [lactate]i. Similarly, an increase was recorded in primary rat astrocytes, a type of neuroglial cell abundant in the brain, which contain glycogen and express enzymes of aerobic glycolysis. In CRISPR-Cas9 GPR27 knocked out 3T3 cells, the 8535-induced increase in [lactate]i was reduced compared with WT controls. Transfection of the GPR27-carrying plasmid into the 3T3KOGPR27 cells rescued the 8535-induced increase in [lactate]i. These results indicate that stimulation of GPR27 enhances aerobic glycolysis and L-lactate production in 3T3 cells and astrocytes. Interestingly, in the absence of GPR27 in 3T3 cells, resting [lactate]i was increased in comparison with controls, further supporting the view that GPR27 regulates L-lactate homeostasis.

Keywords

3T3 embrionalne celice;astrociti;aerobna glikoliza;3T3 embryonic cells;astrocytes;aerobic glycolysis;

Data

Language: English
Year of publishing:
Typology: 1.01 - Original Scientific Article
Organization: UL MF - Faculty of Medicine
UDC: 616
COBISS: 101228291 Link will open in a new window
ISSN: 2073-4409
Views: 75
Downloads: 23
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Other data

Secondary language: Slovenian
Secondary keywords: 3T3 embrionalne celice;astrociti;aerobna glikoliza;
Type (COBISS): Article
Pages: str. 1-14
Volume: ǂVol. ǂ11
Issue: ǂiss. ǂ6
Chronology: 2022
DOI: 10.3390/cells11061009
ID: 15702046