Review: The HSP90 molecular chaperone—an enigmatic ATPase

Pearl, Laurence H.

doi:10.1002/bip.22835

Cited by 159 publications

(133 citation statements)

References 104 publications

(139 reference statements)

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“…More specifically, p44/42MAPK modulates cell functions of gene expression, cell proliferation/differentiation, and cell survival or apoptosis [29, 30]. Hsp90 refers to a chaperone protein that aids in other molecules to fold properly, and to stabilize proteins against heat stress, and it also regulates a group of proteins required for cell growth [31], as well as aids in intracellular transport, degradation of protein and facilitating cell signaling [32]. Thus, we extrapolate that Hsp90 biomolecule may respond to early liver injury under drug-induced effects.…”

Section: Discussionmentioning

confidence: 99%

Biocharacterization of Heat Shock Protein 90 in Acetaminophen-Treated Livers Without Conspicuous Drug Induced Liver Injury

Wu¹,

Guo²,

Su³

et al. 2017

Cell Physiol Biochem

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Background/Aims: Acetaminophen (APAP) refers to a medication used to manage pain and fever symptoms. Heat shock protein 90 (Hsp90) is to be expressed during various stresses, such as wound healing and tissue remodeling. Recently, it is discovered that Hsp90 is a potential modifier of cytogenesis. In comparison to clinical references of liver damage, this study was designed to assess the potential bioeffect of Hsp90 in APAP-treated livers without conspicuous drug induced liver injury (DILI). Methods: In our current study, human plasma samples of APAP-used patients were collected for biochemical assays in clinical parameters. Adult male mice were used to investigate the biocharacterization of Hsp90 in APAP-treated livers through serological tests and immunoassays. Further, a mouse liver cell strain was employed in assessment of bioeffect of APAP on hepatocellular Hsp90 expression. Results: Correspondingly, the clinical data showed APAP-administered patients resulted in increased Hsp90 levels in serum when compared to other clinical parameters of liver injury. In adult mice study, APAP-treated livers showed unchanged hepatocellular and metabolic functions, as highlighted in biochemical analysis and immunoassay. Notably, Hsp90 expression in APAP-treated mice were elevated in the serum and liver samples. In quantitative western blot assay, the present data suggested that hepatocellular Hsp90 level was up-regulated followed by APAP treatment. In mouse cell strain study, APAP-treated liver cells had increased trend of aminotransferase contents and apoptotic counts. Further, endogenous Hsp90 expression in APAP-exposed cells was increased dose- and time-dependently. Conclusions: In conclusion, our current findings disclose that Hsp90 biomolecule may be a potential indicator for APAP-induced inconspicuous DILI, in which it seems to be characterized with more sensitive than other diagnosis criteria.

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Section: Discussionmentioning

confidence: 99%

Biocharacterization of Heat Shock Protein 90 in Acetaminophen-Treated Livers Without Conspicuous Drug Induced Liver Injury

Wu¹,

Guo²,

Su³

et al. 2017

Cell Physiol Biochem

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“…462,463 Because many Hsp90 client proteins are in oncogenic signaling pathways, Hsp90 was proposed as a therapeutic target for anticancer strategies. 464 Geldanamycin is a naturally occurring antibiotic, with Hsp90 identified as its molecular target.…”

Section: Mitochondria-targeted Bioactive Compounds As Potential Thmentioning

confidence: 99%

Mitochondria-Targeted Triphenylphosphonium-Based Compounds: Syntheses, Mechanisms of Action, and Therapeutic and Diagnostic Applications

Zielonka¹,

Joseph²,

et al. 2017

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Mitochondria are recognized as one of the most important targets for new drug design in cancer, cardiovascular, and neurological diseases. Currently, the most effective way to deliver drugs specifically to mitochondria is by covalent linking a lipophilic cation such as an alkyltriphenylphosphonium moiety to a pharmacophore of interest. Other delocalized lipophilic cations, such as rhodamine, natural and synthetic mitochondria-targeting peptides, and nanoparticle vehicles, have also been used for mitochondrial delivery of small molecules. Depending on the approach used, and the potentials of cell and mitochondrial membranes, more than 1000-fold higher mitochondrial concentration can be achieved. Mitochondrial targeting has been developed to study mitochondrial physiology and dysfunction and the interaction between mitochondria and other subcellular organelles and for treatment of a variety of diseases such as neurodegeneration and cancer. In this review, we discuss efforts to target small-molecule compounds to mitochondria for probing mitochondria function, as diagnostic tools and potential therapeutics. We describe the physicochemical basis for mitochondrial accumulation of lipophilic cations, synthetic chemistry strategies to target compounds to mitochondria, mitochondrial probes and sensors, and examples of mitochondrial targeting of bioactive compounds. Finally, we review published attempts to apply mitochondria-targeted agents for the treatment of cancer and neurodegenerative diseases.

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“…We further move our focus to HSP90, a chaperone protein that facilities other proteins folding properly, stabilizes protein against stimulations, and rescues protein from degradation [16]. HSP90 is normally required for protein stabilization essential to tumour progress [16].…”

Section: Discussionmentioning

confidence: 99%

“…HSP90 is normally required for protein stabilization essential to tumour progress [16]. Therefore, the protein is always considered as a drug target for cancer therapy and research [17].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of HSP90 Promotes Neural Stem Cell Survival from Oxidative Stress through Attenuating NF‐κB/p65 Activation

Liu

Jiang

et al. 2016

Oxidative Medicine and Cellular Longevity

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Stem cell survival after transplantation determines the efficiency of stem cell treatment, which develops as a novel potential therapy for several central nervous system (CNS) diseases in recent decades. The engrafted stem cells face the damage of oxidative stress, inflammation, and immune response at the lesion point in host. Among the damaging pathologies, oxidative stress directs stem cells to apoptosis and even death through several signalling pathways and DNA damage. However, the in-detail mechanism of stem cell survival from oxidative stress has not been revealed clearly. Here, in this study, we used hydrogen peroxide (H2O2) to induce the oxidative damage on neural stem cells (NSCs). The damage was in consequence demonstrated involving the activation of heat shock protein 90 (HSP90) and NF-κB/p65 signalling pathways. Further application of the pharmacological inhibitors, respectively, targeting at each signalling indicated an upper-stream role of HSP90 upon NF-κB/p65 on NSCs survival. Preinhibition of HSP90 with the specific inhibitor displayed a significant protection on NSCs against oxidative stress. In conclusion, inhibition of HSP90 would attenuate NF-κB/p65 activation by oxidative induction and promote NSCs survival from oxidative damage. The HSP90/NF-κB mechanism provides a new evidence on rescuing NSCs from oxidative stress and also promotes the stem cell application on CNS pathologies.

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Review: The HSP90 molecular chaperone—an enigmatic ATPase

Cited by 159 publications

References 104 publications

Biocharacterization of Heat Shock Protein 90 in Acetaminophen-Treated Livers Without Conspicuous Drug Induced Liver Injury

Biocharacterization of Heat Shock Protein 90 in Acetaminophen-Treated Livers Without Conspicuous Drug Induced Liver Injury

Mitochondria-Targeted Triphenylphosphonium-Based Compounds: Syntheses, Mechanisms of Action, and Therapeutic and Diagnostic Applications

Inhibition of HSP90 Promotes Neural Stem Cell Survival from Oxidative Stress through Attenuating NF‐κB/p65 Activation

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