4-N,N-dipropylaminobenzaldehyde inhibits the oxidation of all-trans retinal to all-trans retinoic acid by ALDH1A1, but not the differentiation of HL-60 promyelocytic leukemia cells exposed to all-trans retinalReportar como inadecuado




4-N,N-dipropylaminobenzaldehyde inhibits the oxidation of all-trans retinal to all-trans retinoic acid by ALDH1A1, but not the differentiation of HL-60 promyelocytic leukemia cells exposed to all-trans retinal - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

BMC Pharmacology

, 2:4

First Online: 12 February 2002Received: 20 July 2001Accepted: 12 February 2002

Abstract

BackgroundThe signal transduction pathways mediated by retinoic acid play a critical role in the regulation of cell growth and differentiation during embryogenesis and hematopoiesis as well as in a variety of tumor cell lines in culture. Following the reports that two members of the superfamily of aldehyde dehydrogenase ALDH enzymes, ALDH1A1 and ALDH1A2, were capable of catalyzing the oxidation of all-trans retinal to all-trans retinoic acid with submicromolar Km values, we initiated an investigation of the ability of 4-N,N-dipropylaminobenzaldehyde DPAB to inhibit the oxidation of retinal by purified mouse and human ALDH1A1.

ResultsOur results show that DPAB potently inhibits retinal oxidation, with IC50 values of 0.11 and 0.13 μM for purified mouse and human ALDH1A1, respectively. Since the HL-60 human myeloid leukemic cell line has been used extensively to study the retinoic acid induced differentiation of HL-60 cells to granulocytes, and ALDH1A1 activity had previously been reported in HL-60 cells, we investigated the ability of DPAB to block differentiation of HL-60 promyelocytic leukemia cells exposed to retinal in culture. In HL-60 cells coincubated with 1 μM retinal and 50 μM DPAB for 144 hours, cell differentiation was inhibited only 30%. Furthermore, the NAD-dependent oxidation of propanal or retinal was less than 0.05 nmoles NADH formed-min-10 cells in spectrophotometric assays using HL-60 cell extracts.

ConclusionAlthough ALDH1A1 may be the major catalytic activity for retinal oxidation in some retinoid-dependent mouse and Xenopus embryonic tissues and in adult human and mouse hematopoietic stem cells, another catalytic activity appears to synthesize the retinoic acid ligand necessary to stimulate the differentiation of HL-60 cells to end stage granulocytes.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2210-2-4 contains supplementary material, which is available to authorized users.

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Autor: James Russo - Annette Barnes - Katie Berger - Jay Desgrosellier - Jennifer Henderson - Ana Kanters - Lubo Merkov

Fuente: https://link.springer.com/







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