13,14-Dihydroxy-retinol, a new bioactive retinol metabolite.
Deprivation of vitamin A (retinol) leads to reduced potential of B cell proliferation and nearly complete block of T cell activation in vitro. Retinol, which is thought to function as a pro-hormone, is enzymatically converted into intracellular messenger molecules. Thus, 14-hydroxy-retro-retinol (14-HRR) is an intracellular messenger molecule linked to activation and growth regulation of lymphocytes; whereas, anhydroretinol, another natural retro-retinoid, is an antagonist of 14-HRR effects. In this article, we describe the isolation, structure determination, synthesis, and biological properties of a new intracellular retinol derivative, 13,14-dihydroxy-retinol (DHR), which also supports the viability of retinol-deprived lymphocytes. DHR is found in numerous cell lines representing a large cross-section of tissues and animals from insects to mammals. In T lymphocytes the production of DHR and 14-HRR is up-regulated by phorbol ester. DHR is converted to 14-HRR by mild acid treatment, but not by cells; therefore DHR is not a biosynthetic intermediate in the conversion of retinol to 14-HRR. DHR is a distinct end point of retinol metabolism. Although it is linked to cell proliferation, its biological role remains to be determined.
Derguini
F
F
Department of Chemistry, Columbia University, New York, New York 10027, USA.
Nakanishi
K
K
Hämmerling
U
U
Chua
R
R
Eppinger
T
T
Levi
E
E
Buck
J
J
D002460:Cell Line; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D014801:Vitamin A / Q000378:metabolism*
D014801:Vitamin A