Aldo-keto reductase family 1 member B8 is secreted via non-classical pathway

Mouse aldo-keto reductase family 1 member B8 (AKR1B8) has the highest similarity to human aldo-keto reductase family 1 member B10 (AKR1B10), a secretory protein through lysosomes-mediated non-classical secretory pathway. To identify whether AKR1B8 is secreted through the same pathway, we carried out this study. Self-developed sandwich ELISA and western blot were used to detect AKR1B8 in cells and culture medium of CT-26 murine colon carcinoma cells. AKR1B8 releases in an independent manner to Brefeldin A, an inhibitor of ER-to-Golgi classical secretion pathway. Several factors, which are involved in the non-classical secretion pathway, such as temperature, ATP and calcium ion, regulated AKR1B8 secretion from mouse colorectal cancer cells CT-26. Lysosomotropic NH4Cl increased AKR1B8 secretion, and AKR1B8 was located in isolated lysosomes. Therefore, AKR1B8 is a new secretory protein through the lysosomes-mediated non-classical pathway.