Retinol but not retinoic acid can enhance the glutathione level, in a manner similar to β‐carotene, in a murine cultured macrophage cell line

SCOPE: We evaluated the potential of retinol and retinoic acid (RA) to enhance intracellular glutathione (GSH) levels in a murine cultured macrophage cell line, RAW264, to investigate whether the RA signaling pathway is involved in the β‐carotene‐induced GSH enhancement. METHODS AND RESULTS: We examined GSH levels in RAW264 cells cultured in media supplemented with β‐carotene and various inhibitors (ER50891 for RA receptor (RAR)α, CD2665 for RARβ/γ, or HX531 for all subtypes of retinoid X receptor (RXR)), to verify each inhibitor's activity against β‐carotene, as well as in media supplemented with various stimulants (AM80 for RARα, CD2314 for RARβ, CD437 for RARγ, or SR11237 for RXR), to compare their activity with that of β‐carotene. We also examined the GSH level and glutamate‐cysteine‐ligase (GCL) expression in RAW264 cells cultured in all‐trans RA‐ or retinol‐supplemented media. Enhanced GSH production was not inhibited by any tested antagonist, and, apart from β‐carotene, no agonist induced GSH production. Retinol, but not all‐trans RA, enhanced GSH synthesis and increased GCL expression, similar to that observed with β‐carotene. CONCLUSION: The RA signaling pathway may not be involved in the β‐carotene‐induced enhancement of GSH levels in RAW264 cells, whereas, like β‐carotene, retinol can enhance the GSH level and GCL expression.