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Differential effects of 9-cis and all-trans retinoic acid on the induction of retinoic acid receptor-beta and cellular retinoic acid-binding protein II in human neuroblastoma cells

Lookup NU author(s): Dr Chris Redfern, Professor Penny Lovat, Professor Archibald Malcolm, Professor Andrew Pearson

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Abstract

The objective of this study was to compare the properties of 9-cis and all-trans retinoic acid with respect to the induction of expression of retinoic acid receptor beta (RAR-beta) and cellular retinoic acid-binding protein (CRABP) II in human neuroblastoma SH SY 5Y cells. RAR-beta and CRABP II mRNA was induced by both all-trans and 9-cis retinoic acid in SH SY 5Y cells. Induction was rapid, detectable within 2-4 h, and inhibited by actinomycin D. Time-courses of induction for RAR-beta and CRABP II differed: RAR-beta mRNA levels reached a maximum 4-6 h after adding all-trans or 9-cis retinoic acid, whereas CRABP II mRNA levels increased over at least 18 h. These differences were attributed to the longer half-life of CRABP II mRNA (20 h) compared with RAR-beta mRNA (3.9 h). The dose-response characteristics of all-trans and 9-cis retinoic acid were different: all-trans was effective at nanomolar concentrations, whereas 10-fold higher levels of 9-cis retinoic acid were required to achieve comparable induction of RAR-beta and CRABP II. Conversely, at high concentrations, 9-cis retinoic acid gave a greater induction of RAR-beta and CRABP II than all-trans. The induction of RAR-beta and CRABP II by all-trans retinoic acid was maintained in the subsequent absence of all-trans retinoic acid, whereas induction by 9-cis retinoic acid was dependent on its continued presence in the culture medium. These results suggest that, at high concentrations, 9-cis retinoic acid may produce its transcriptional effects via retinoid X receptor (RXR) homodimers. This has implications for the cellular functions of 9-cis retinoic acid and its use as a biological response modifier.


Publication metadata

Author(s): Redfern CPF, Lovat PE, Malcolm AJ, Pearson ADJ

Publication type: Article

Publication status: Published

Journal: Biochemical Journal

Year: 1994

Volume: 304

Issue: part 1

Pages: 147-154

Print publication date: 01/11/1994

ISSN (print): 0264-6021

ISSN (electronic): 1470-8728

URL: http://www.biochemj.org/bj/304/bj3040147.htm

PubMed id: 7998926


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