regulation of mouse small heat shock protein αb-crystallin gene by aryl hydrocarbon receptor调节老鼠小热休克蛋白αb-crystallin芳基碳氢化合物受体基因.pdfVIP

Regulation of Mouse Small Heat Shock Protein ab- Crystallin Gene by Aryl Hydrocarbon Receptor 1,2 1 Shuang Liu *, Joram Piatigorsky * 1 Laboratory of Molecular and Developmental Biology, National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States of America, 2 Laboratory of Experimental Immunology, National Cancer Institute, National Institutes of Health, Frederick, Maryland, United States of America Abstract The stress-inducible small heat shock protein (shsp)/aB-crystallin gene is expressed highly in the lens and moderately in other tissues. Here we provide evidence that it is a target gene of the aryl hydrocarbon receptor (AhR) transcription factor. A sequence (2329/ 2323, CATGCGA) similar to the consensus xenobiotic responsive element (XRE), called here XRE-like, is present in the aBE2 region of aB-crystallin enhancer and can bind AhR in vitro and in vivo. aB-crystallin protein levels were reduced in retina, lens, cornea, heart, skeletal muscle and cultured muscle fibroblasts of AhR 2/ 2 mice; aB-crystallin mRNA levels were reduced in the eye, heart and skeletal muscle of AhR 2/ 2 mice. Increased AhR stimulated aB-crystallin expression in transfection experiments conducted in conjunction with the aryl hydrocarbon receptor nuclear translocator (ARNT) and decreased AhR reduced aB-crystallin expression. AhR effect on aB-crystallin promoter activity was cell-dependent in transfection experiments. AhR up-regulated aB-crystallin promoter activity in transfected HeLa, NIH3T3 and COS-7 cells in the absence of exogenously added ligand (TCDD), but had no effect on the aB-crystallin promoter in C2C12, CV-1 or Hepa-1 cells with or without TCDD. TCDD enhanced AhR-stimulated aB-crystallin promoter activity in transfected aTN4 cells. AhR co