[Molecular chaperone Hsp70 protects neuroblastoma SK-N-SH cells from hypoxic stress].
HIF-1alpha is synthesized constutively, however under normoxia it is specifically degraded. Hypoxia blocks the factor degradation, and it activates the transcription of genes whose products control multiple cellular processes. Hsp70 molecular chaperone is known to protect neural cells from the deleterious effects of hypoxic stress, though the mechanism of this action remains elusive. To understand how Hsp70 protects cells affected by hard hypoxia the model cell line was constructed based on human neuroblastoma SK-N-SH cells and over-expressing the chaperone when treated by zinc salt. The cells were shown to be resistant to the treatment by CoCl2 imitating in the experiments the reaction to hypoxia. Life span of HIF-1alpha was elevated in these cells as compared with parental line due to the fact that Hsp70 formed long-time complex with HIF-1alpha. The data show that Hsp70 interferes with signaling pathways of cellular response to hypoxic stress at the level of regulation of HIF-1alpha stability.
Tikhonova
N S
NS
Moskaleva
O S
OS
Margulis
B A
BA
Guzhova
I V
IV
D045744:Cell Line, Tumor; D003035:Cobalt / Q000009:adverse effects; D018840:HSP70 Heat-Shock Proteins / Q000502:physiology*; D006801:Humans; D000860:Hypoxia / Q000139:chemically induced / Q000503:physiopathology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis; D015398:Signal Transduction / Q000502:physiology
D018840:HSP70 Heat-Shock Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D011994:Recombinant Proteins; D003035:Cobalt; C018021:cobaltous chloride