The role of tonicity responsive enhancer sites in the transcriptional regulation of human hsp70-2 in response to hypertonic stress

다국어 초록 (Multilingual Abstract)

The inducible 70 kDa heat shock proteins (Hsp70) in mice are encoded by two almost identical genes, hsp70.1 and hsp70.3. Studies have found that only hsp70.1 is induced by hypertonic stress while both hsp70.1 and hsp70.3 genes are expressed in response to heat shock stress. It is unclear if the human counterparts, hsp70-2 and hsp70-1, are differentially regulated by heat shock and osmotic hsp70-2 was induced by hypertonic stress in human embryonic kidney epithelial cells and fibroblasts, while heat shock stress induced both hsp70-1 and hsp70-2. The human hsp70-2 promoter region contains three TonE (tonicity-responsive enhancer) sites, which were reported to play an important role in the response to hypertonicity. When the reporter plasmids contain-ing different parts of the 5' flanking region of hsp70-2 were transfected into human embryonic kidney epithelial cells or fibroblasts, one TonE site at -135 was found to play a key role in the response to hypertonicity. The inactivation of the TonE site using of induction by hypertonicity, which demonstrates the essential role of the TonE site. This suggests that the TonE site and the TonEBP (TonE binding protein) are the major regulators for the cellular response against high osmolarity in human kidney tissue.

참고문헌 (Reference)

1 "Transcriptional regu-lation of heat shock genes A paradigm for inducible genomic responses" 21987-90,

2 "Transcription of the sodium/myo-inositol cotransporter gene is regulated by multiple tonicity-responsive enhancers spread over 50 kilobase pairs in the 5'-flanking region" 273 : 20615-21, 1998

3 "The expression of heat shock protein 70 decreases with cellular senescence in vitro and in cells derived from young and old hu-man subjects" 241 : 404-13, 1998

4 "Targeted disruption of hsp70 1 sensitizes to osmotic stress" 3 : 857-61, 2002

5 "T cell lymphoma in transgenic mice expressing the human Hsp70 gene" 218 : 582-7, 1996

6 "Stress management - heat shock pro-tein-70 and the regulation of apoptosis" 11 : 6-10, 2001

7 "Stabilization of hsp70 mRNA on prolonged cell exposure to hypertonicity" 1592 : 135-40, 2002

8 "Serum and lymphocyte levels of heat shock protein 70 in aging a study in the normal Chinese population" 9 : 69-75, 2004

9 "Role of the human heat shock protein hsp70 in protection against stress-induced apoptosis" 17 : 5317-27, 1997

10 "Role of the heat shock response and mo-lecular chaperones in oncogenesis and cell death" 92 : 1564-72, 2000

11 "Negative regulation of the Apaf-1 apoptosome by Hsp70." 2 : 476-83, 2000

12 "Major heat shock pro-tein hsp70 protects tumor cells from tumor necrosis factor cytotoxicity" 3507-12, emboj1992;11

13 "Identification of the second tonicity-responsive enhancer for the betaine trans-porter (BGT1) gene." 1446 : 359-64, 1999

14 "Hypertonic stress response" 569 : 65-74, 2005

15 "Human aging alters the first phase of the molecular response to stress in T-cells" 40 : 948-58, 2005

16 "Heat-shock protein 70 inhibits apoptosis by preventing recruitment of pro-caspase-9 to the Apaf-1 apoptosome" 2 : 469-75, 2002

17 "Heat shock protein 70 inhibits apoptosis downstream of cytochrome c release and upstream of caspase-3 activation" 275 : 25665-71, 2000

18 "Diferential expression of two stress-inducible hsp70 genes by various stressors" 34 : 131-6, 2002

19 "Cyclosporine A inhibits the adaptive responses to hypertonicity: a potential mechanism of nephro-toxicity." 12 : 2732-41, 2001

20 "Chaperone-mediated protein folding" 79 : 425-49, 1999

21 "Age-re-lated decrease in the inductability of heat shock protein 72 in normal human skin" 134 : 1035-8, 1996