Targeted disruption of hsp70.1 sensitizes to osmotic stress.
The 70 kDa heat shock protein (Hsp70) plays a critical role in cell survival and thermotolerance in response to various stress stimuli. Two nearly identical genes, hsp70.1 and hsp70.3, in response to environmental stress, rapidly induce Hsp70. However, it remains unclear whether these two genes are differentially regulated by various stresses. To address the physiological role of the hsp70.1 and hsp70.3 genes in the stress response, we generated mice that specifically lack hsp70.1. In contrast to heat shock, which rapidly induced both hsp70.1 and hsp70.3 mRNA, osmotic stress selectively induced transcription of hsp70.1. In hsp70.1-deficient embryonic fibroblasts, osmotic stress markedly reduced cell viability. Furthermore, when osmotic stress was applied in vivo, hsp70.1-deficient mice exhibited increased apoptosis in the renal medulla. Taken together, our results demonstrate that differential expression of hsp70 genes contributes to the stress response and that the hsp70.1 gene plays a critical role in osmotolerance.
Shim
Eun-Hee
EH
Department of Biochemistry and ILCHUN Molecular Medicine Institute MRC, Seoul National University College of Medicine, Korea.
Kim
Jong-Il
JI
Bang
Eui-Suk
ES
Heo
Jun-Seok
JS
Lee
Jae-Seon
JS
Kim
Eun-Young
EY
Lee
Jong-Eun
JE
Park
Woong-Yang
WY
Kim
Soon-Hee
SH
Kim
Hyung-Suk
HS
Smithies
Oliver
O
Jang
Ja-Joon
JJ
Jin
Dong-Il
DI
Seo
Jeong-Sun
JS
D020413:3' Untranslated Regions; D000818:Animals; D017209:Apoptosis; D015152:Blotting, Northern; D015153:Blotting, Western; D002470:Cell Survival; D002478:Cells, Cultured; D005821:Genetic Techniques; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics*; D020287:In Situ Nick-End Labeling; D051379:Mice; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D016297:Mutagenesis, Site-Directed; D009997:Osmotic Pressure; D015800:Protozoan Proteins / Q000235:genetics*; D013997:Time Factors
D020413:3' Untranslated Regions; D018840:HSP70 Heat-Shock Proteins; D015800:Protozoan Proteins; C081884:heat-shock protein 70.1