TSPO2 translocates 5‐aminolevulinic acid into human erythroleukemia cells. (5th February 2020)

• Record Type: Journal Article
• Authors: Manceau, Hana; Lefevre, Sophie D; Mirmiran, Arienne; Hattab, Claude; Sugier, Hugo R; Schmitt, Caroline; Peoc'h, Katell; Puy, Hervé; Ostuni, Mariano A; Gouya, Laurent; Lacapere, Jean‐Jacques
• Is Part Of: Biology of the cell. Volume 112:Number 4(2020)
• Page Start: 113
• Page End: 126
• Publication Date: 2020-02-05
• Subjects: Membrane protein -- Membrane transport -- Metabolism -- Transporters; Cytology -- Periodicals; Electron microscopy -- Periodicals; 571.6
• DOI: 10.1111/boc.201900098
• Languages: English
• ISSNs: 0248-4900

Abstract

Abstract : Background: 5‐Aminolevulinic acid (ALA) is the first precursor of heme biosynthesis pathway. The exogenous addition of ALA to cells leads to protoporphyrin IX (PPIX) accumulation that has been exploited in photodynamic diagnostic and photodynamic therapy. Several types of ALA transporters have been described depending on the cell type, but there was no clear entry pathway for erythroid cells. The 18 kDa translocator protein (TSPO) has been proposed to be involved in the transport of porphyrins and heme analogs. Results: ALA‐induced PPIX accumulation in erythroleukemia cells (UT‐7 and K562) was impaired by PK 11195, a competitive inhibitor of both transmembrane proteins TSPO (1 and 2). PK 11195 did not modify the activity of the enzymes of heme biosynthesis, suggesting that ALA entry at the plasma membrane was the limiting factor. In contrast, porphobilinogen (PBG)‐induced PPIX accumulation was not affected by PK 11195, suggesting that plasma membrane TSPO2 is a selective transporter of ALA. Overexpression of TSPO2 at the plasma membrane of erythroleukemia cells increased ALA‐induced PPIX accumulation, confirming the role of TSPO2 in the import of ALA into the cells. Conclusions: ALA‐induced PPIX accumulation in erythroid cells involves TSPO2 as a selective translocator through the plasma membrane. Significance: This is the first characterisation of molecular mechanisms involving a new actor in ALA transport in ALA‐induced PPIX accumulation in erythroleukemia cells, which could be inhibited by specific drug ligands. Abstract : Research article : 5‐Aminolevulinic acid (ALA), the first intermediate in heme biosynthesis pathway, is used to increase protoporphyrin (PRIX) content of cell before photoirradiation in phototherapy. TSPO2, a transmembrane protein located at the plasma membrane of erythroblasts and mature red blood cell, is involved in ALA transport, inhibited by PK 11195, specific to TSPO ligand.