Abstract | BACKGROUND: RESULTS: Our results show that DPAB potently inhibits retinal oxidation, with IC50 values of 0.11 and 0.13 microM 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 microM retinal and 50 microM 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(7) cells in spectrophotometric assays using HL-60 cell extracts. CONCLUSION: Although 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.
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Authors | James Russo, Annette Barnes, Katie Berger, Jay Desgrosellier, Jennifer Henderson, Ana Kanters, Lubo Merkov |
Journal | BMC pharmacology
(BMC Pharmacol)
Vol. 2
Pg. 4
( 2002)
ISSN: 1471-2210 [Electronic] England |
PMID | 11872149
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Benzaldehydes
- Isoenzymes
- Tretinoin
- 4-(N,N-dipropylamino)benzaldehyde
- Aldehyde Dehydrogenase 1 Family
- Aldehyde Dehydrogenase
- ALDH1A1 protein, human
- ALDH1A1 protein, mouse
- Retinal Dehydrogenase
- Retinaldehyde
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Topics |
- Aldehyde Dehydrogenase
(metabolism)
- Aldehyde Dehydrogenase 1 Family
- Animals
- Benzaldehydes
(pharmacology)
- Cell Differentiation
(drug effects)
- HL-60 Cells
- Humans
- Isoenzymes
(metabolism)
- Mice
- Oxidation-Reduction
(drug effects)
- Retinal Dehydrogenase
- Retinaldehyde
(metabolism)
- Tretinoin
(metabolism)
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