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Effect of acetaldehyde on Sp1 binding and activation of the mouse alpha 2(I) collagen promoter.
Arch Biochem Biophys. 1997 May 01; 341(1):140-52.AB

Abstract

Acetaldehyde activates the mouse alpha 2(I) collagen promoter and this effect is mediated in part by increased binding of nuclear factor I (NF-I). Additional mechanisms may exist since deletions in the promoter upstream to the NF-I binding site prevented enhancement by acetaldehyde. Three adjacent areas of binding by nuclear proteins from activated hepatic stellate cells were identified at -568 to -554 (region 1), -542 to -518 (region 2), and -473 to -453 (region 3) of the promoter using DNase I protection analyses. Multiple DNA-protein complexes were formed in electrophoretic mobility shift assays with oligonucleotide probes specifying the three regions. Sp1 and NF-1 bound to all three regions, while Sp3 bound to region 2. Acetaldehyde decreased nuclear protein binding to all three regions. Mutations of regions 1, 2, and 3 reduced basal activity of the promoter and inhibited acetaldehyde stimulation in transfected stellate cells. Acetaldehyde inhibited the stimulatory effect of the Sp1 vector pPacSp1 on the promoter in transfected Drosophila cells. In conclusion, three regions of Sp1 binding were identified and are required for optimal activity of the alpha 2(I) collagen promoter. Sp1 is required for basal activity of the alpha 2(I) collagen promoter; however, the enhancing effect of acetaldehyde on the promoter is not mediated by Sp1.

Authors+Show Affiliations

Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2195, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

9143363

Citation

Miao, K, et al. "Effect of Acetaldehyde On Sp1 Binding and Activation of the Mouse Alpha 2(I) Collagen Promoter." Archives of Biochemistry and Biophysics, vol. 341, no. 1, 1997, pp. 140-52.
Miao K, Potter JJ, Anania FA, et al. Effect of acetaldehyde on Sp1 binding and activation of the mouse alpha 2(I) collagen promoter. Arch Biochem Biophys. 1997;341(1):140-52.
Miao, K., Potter, J. J., Anania, F. A., Rennie-Tankersley, L., & Mezey, E. (1997). Effect of acetaldehyde on Sp1 binding and activation of the mouse alpha 2(I) collagen promoter. Archives of Biochemistry and Biophysics, 341(1), 140-52.
Miao K, et al. Effect of Acetaldehyde On Sp1 Binding and Activation of the Mouse Alpha 2(I) Collagen Promoter. Arch Biochem Biophys. 1997 May 1;341(1):140-52. PubMed PMID: 9143363.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of acetaldehyde on Sp1 binding and activation of the mouse alpha 2(I) collagen promoter. AU - Miao,K, AU - Potter,J J, AU - Anania,F A, AU - Rennie-Tankersley,L, AU - Mezey,E, PY - 1997/5/1/pubmed PY - 1997/5/1/medline PY - 1997/5/1/entrez SP - 140 EP - 52 JF - Archives of biochemistry and biophysics JO - Arch Biochem Biophys VL - 341 IS - 1 N2 - Acetaldehyde activates the mouse alpha 2(I) collagen promoter and this effect is mediated in part by increased binding of nuclear factor I (NF-I). Additional mechanisms may exist since deletions in the promoter upstream to the NF-I binding site prevented enhancement by acetaldehyde. Three adjacent areas of binding by nuclear proteins from activated hepatic stellate cells were identified at -568 to -554 (region 1), -542 to -518 (region 2), and -473 to -453 (region 3) of the promoter using DNase I protection analyses. Multiple DNA-protein complexes were formed in electrophoretic mobility shift assays with oligonucleotide probes specifying the three regions. Sp1 and NF-1 bound to all three regions, while Sp3 bound to region 2. Acetaldehyde decreased nuclear protein binding to all three regions. Mutations of regions 1, 2, and 3 reduced basal activity of the promoter and inhibited acetaldehyde stimulation in transfected stellate cells. Acetaldehyde inhibited the stimulatory effect of the Sp1 vector pPacSp1 on the promoter in transfected Drosophila cells. In conclusion, three regions of Sp1 binding were identified and are required for optimal activity of the alpha 2(I) collagen promoter. Sp1 is required for basal activity of the alpha 2(I) collagen promoter; however, the enhancing effect of acetaldehyde on the promoter is not mediated by Sp1. SN - 0003-9861 UR - https://www.unboundmedicine.com/medline/citation/9143363/Effect_of_acetaldehyde_on_Sp1_binding_and_activation_of_the_mouse_alpha_2_I__collagen_promoter_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0003-9861(97)99948-3 DB - PRIME DP - Unbound Medicine ER -