Comparison of the distribution of glial fibrillary acidic protein, heat shock protein 60, and hypoxia-inducible factor-1α in retinas from glaucomatous and normal canine eyes

2008 ◽  
Vol 69 (2) ◽  
pp. 265-272 ◽  
Author(s):  
Caitlin A. Savagian ◽  
Richard R. Dubielzig ◽  
T. Michael Nork
Keyword(s):  
Heat Shock ◽  
Glial Fibrillary Acidic Protein ◽  
Heat Shock Protein ◽  
Hypoxia Inducible Factor ◽  
Acidic Protein ◽  
Heat Shock Protein 60 ◽  
Hypoxia Inducible Factor 1Α

Identification of heat shock protein 60 as the regulator of the hypoxia-inducible factor subunit HIF-1α

2012 ◽  
Vol 84 (11) ◽  
pp. 2325-2337 ◽  
Author(s):  
Hyun Seung Ban ◽  
Kazuki Shimizu ◽  
Hidemitsu Minegishi ◽  
Hiroyuki Nakamura
Keyword(s):  
Growth Factor ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Click Reaction ◽  
Photoaffinity Labeling ◽  
Hypoxia Inducible Factor ◽  
Fluorescent Imaging ◽  
Target Protein ◽  
Heat Shock Protein 60 ◽  
Pathological Angiogenesis

The hypoxia-inducible factor (HIF) takes part in transcriptional activation of hypoxia-responsive genes such as vascular endothelial growth factor (VEGF), insulin-like growth factor, and inducible nitric oxide synthase. Since VEGF plays an important role in pathological angiogenesis such as tumor growth and ischemic diseases, the inhibition of VEGF inducer HIF is an attractive approach for the inhibition of pathological angiogenesis. Recently, we have reported that the introduction of boronic acid and a carborane moiety into phenoxyacetanilide induced a potent inhibitory effect on HIF-1α activation under hypoxic conditions. In the present study, to clarify the mechanism of action of carboranylphenoxyacetanilide GN26361 against HIF inhibition, we designed and synthesized molecular probes of GN26361 substituted with benzophenone to induce covalent binding with the target protein by UV (photoaffinity labeling) and an acetylenic moiety to conjugate with the green-fluorescent Alexa Fluor 488-azide by click reaction. In-gel fluorescent imaging of target protein bound with the probe was identified as heat shock protein 60 (HSP60). Moreover, direct binding in gel fluorescent imaging was observed by photoaffinity labeling and click reaction of the probe with recombinant HSP60. These results indicate that HSP60 is the target protein of GN26361 and might be a new molecular target for HIF inhibition.

scholarly journals Heat Induction of the Unphosphorylated Form of Hypoxia-inducible Factor-1α Is Dependent on Heat Shock Protein-90 Activity

2002 ◽  
Vol 277 (11) ◽  
pp. 9262-9267 ◽  
Author(s):  
Dörthe M. Katschinski ◽  
Lu Le ◽  
Daniel Heinrich ◽  
Klaus F. Wagner ◽  
Thomas Hofer ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Hypoxia Inducible Factor ◽  
Heat Shock Protein 90 ◽  
Heat Induction ◽  
Hypoxia Inducible Factor 1Α

Induction of heat shock protein 70 and glial fibrillary acidic protein in the postischemic gerbil hippocampus

1994 ◽  
Vol 9 (4) ◽  
pp. 369-375 ◽  
Author(s):  
Tsutomu Araki ◽  
Hiroyuki Kato ◽  
Xia-Hong Liu ◽  
Kyuya Kogure ◽  
Yasuo Itoyama
Keyword(s):  
Heat Shock ◽  
Glial Fibrillary Acidic Protein ◽  
Heat Shock Protein ◽  
Heat Shock Protein 70 ◽  
Acidic Protein

scholarly journals A potentially common peptide target in secreted heat shock protein-90α for hypoxia-inducible factor-1α–positive tumors

2012 ◽  
Vol 23 (4) ◽  
pp. 602-613 ◽  
Author(s):  
Divya Sahu ◽  
Zhengwei Zhao ◽  
Fred Tsen ◽  
Chieh-Fang Cheng ◽  
Ryan Park ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Hypoxia Inducible Factor ◽  
Metastatic Breast ◽  
Tumor Formation ◽  
Promoting Effect ◽  
Hypoxia Inducible Factor 1Α ◽  
Amino Acid Region ◽  
Lung Colonization

Deregulated accumulation of hypoxia-inducible factor-1α (HIF-1α) is a hallmark of many solid tumors. Directly targeting HIF-1α for therapeutics is challenging. Our finding that HIF-1α regulates secretion of heat shock protein-90α (Hsp90α) for cell migration raises the exciting possibility that targeting the secreted Hsp90α from HIF-1α–positive tumors has a better clinical outlook. Using the HIF-1α–positive and metastatic breast cancer cells MDA-MB-231, we show that down-regulation of the deregulated HIF-1α blocks Hsp90α secretion and invasion of the cells. Reintroducing an active, but not an inactive, HIF-1α into endogenous HIF-1α–depleted cells rescues both Hsp90α secretion and invasion. Inhibition of Hsp90α secretion, neutralization of secreted Hsp90α action, or removal of the cell surface LRP-1 receptor for secreted Hsp90α reduces the tumor cell invasion in vitro and lung colonization and tumor formation in nude mice. Furthermore, we localized the tumor-promoting effect to a 115–amino acid region in secreted Hsp90α called F-5. Supplementation with F-5 is sufficient to bypass the blockade of HIF-1α depletion and resumes invasion by the tumor cells under serum-free conditions. Because normal cells do not secrete Hsp90α in the absence of stress, drugs that target F-5 should be more effective and less toxic in treatment of HIF-1α–positive tumors in humans.

Sign in / Sign up

Export Citation Format

Share Document