HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Manji, S. S. Articles by Ng, K. W. Search for Related Content PubMed PubMed Citation Articles by Manji, S. S. Articles by Ng, K. W. Social Bookmarking                      What's this?

Volume 270, Number 15, Issue of April 14, pp. 8958-8962, 1995
©1995 by The American Society for Biochemistry and Molecular Biology, Inc.

---

Tumor Necrosis Factor Facilitates Nuclear Actions of Retinoic Acid to Regulate Expression of the Alkaline Phosphatase Gene in Preosteoblasts

Shehnaaz S. Manji , Hong Zhou , David M. Findlay , T. John Martin , Kong Wah Ng

This study examines the molecular mechanisms of interaction between tumor necrosis factor (TNF ) and retinoic acid on the expression of the alkaline phosphatase gene by rat clonal preosteoblastic cells. In this cell line, alkaline phosphatase mRNA was not constitutively expressed but was progressively induced by treatment with 1 µ M retinoic acid, detectable by 6 h. Combining retinoic acid with 0.6 n M TNF resulted in alkaline phosphatase mRNA appearing by 2 h, as well as enhanced expression above that observed with retinoic acid alone at 6, 12, and 24 h. Nuclear run-on analysis showed constitutive transcription of the alkaline phosphatase gene in control and TNF -treated cells. At 4 h, retinoic acid, alone or combined with TNF , increased alkaline phosphatase gene transcriptional rate by 2-fold. However, at 24 h, while no retinoic acid effect was retained, retinoic acid plus TNF resulted in a 5-fold increase in alkaline phosphatase transcriptional rate. Examination of the distribution of nuclear alkaline phosphatase mRNA demonstrated that pre-spliced precursor mRNA was localized to the nuclear matrix in control and all treatment groups. Retinoic acid caused a time-dependent accumulation of mature, spliced alkaline phosphatase mRNA located in the non-matrix and cytoplasmic fractions, implying a post-transcriptional action of retinoic acid in nuclear processing and nucleocytoplasmic transport. Adding TNF with retinoic acid greatly enhanced this effect, which was observed after 4 h, prior to any detectable interaction between TNF and retinoic acid on gene transcription. In sharp contrast, only a negligible amount of nuclear processing occurred in control and TNF -treated cells. This study reveals distinct interactions between TNF and retinoic acid at post-transcriptional as well as transcriptional levels to regulate expression of the alkaline phosphatase gene in preosteoblasts.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				S. Wada, N. Udagawa, T. Akatsu, N. Nagata, T. J. Martin, and D. M. Findlay Regulation by Calcitonin and Glucocorticoids of Calcitonin Receptor Gene Expression in Mouse Osteoclasts Endocrinology, February 1, 1997; 138(2): 521 - 529. [Abstract] [Full Text] [PDF]

				Y. Urata, H. Yamamoto, S. Goto, H. Tsushima, S. Akazawa, S. Yamashita, S. Nagataki, and T. Kondo Long Exposure to High Glucose Concentration Impairs the Responsive Expression of gamma -Glutamylcysteine Synthetase by Interleukin-1beta and Tumor Necrosis Factor-alpha in Mouse Endothelial Cells J. Biol. Chem., June 21, 1996; 271(25): 15146 - 15152. [Abstract] [Full Text] [PDF]