The Protective Role of HSP90 against 3-Hydroxykynurenine-Induced Neuronal Apoptosis

Lee, Myoungwoo; Park, Soon Cheol; Chae, Hee-Sun; Bach, Jae Hyung; Lee, Hyunjung; Lee, Sang Hyung; Kang, Yong Koo; Kim, Kyung Yong; Lee, Won Bok; Kim, Sung Su

doi:10.1006/bbrc.2001.4938

Cited by 52 publications

(31 citation statements)

References 24 publications

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“…Despite the ability of HSP-70 overexpression to protect HK-2 cells, blocking of HSP-70 upregulation with siRNA did not inhibit the protective effect of heat shock. In agreement with our finding, it was reported previously that antisense inhibition of HSP-70 failed to abolish the heat shockinduced protection of neuroblastoma cells from apoptosis (44). We speculate that the heat-shock protective effect that was seen in this study is a multifactorial response to the complex insult of cold storage and rewarming and that a degree of redundancy may exist such that blocking induction of a specific protective factor such as HSP-70 will not blunt the overall protective effect.…”

Section: Discussionsupporting

confidence: 93%

Heat Shock–Induced Protection of Renal Proximal Tubular Epithelial Cells from Cold Storage and Rewarming Injury

Healy¹,

Daly²,

Docherty³

et al. 2006

Journal of the American Society of Nephrology

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Cold storage and reperfusion injury to transplanted kidneys contributes to increased incidence of delayed graft function and may have a negative impact on graft survival. This study examined the mechanisms by which previous heat shock protects against cell death in an in vitro model of kidney storage. Cold storage is mimicked by incubating human renal proximal tubular epithelial (HK-2) cells in University of Wisconsin solution at 4°C with and without subsequent rewarming. Heat shock was induced by incubation of cells at 42°C for 1 h. Altered protein expression was measured by Western blot, and cell viability and apoptosis were measured by propidium iodide DNA staining using flow cytometry. The specific role of heat-shock protein 70 (HSP-70) was determined both by siRNA knockdown and by stable overexpression approaches. Cold storage and rewarming-induced cell death was associated with decreased expression of HSP-70, HSP-90, HSP-27, and Bcl-2. Previous heat shock significantly reduced HK-2 cell death after cold storage and rewarming and was associated with the maintenance of HSP-70, HSP-27, and Bcl-2 protein levels. Blocking heat stress-induced HSP-70 with siRNA did not significantly block the protective effect of heat stress against cold storage and rewarming cell death; however, overexpression of HSP-70 protected HK-2 cells from this stress. It is concluded that previous heat shock protects HK-2 cells from cold storage and rewarming injury. siRNA inhibition of HSP-70 induction did not block the protective effect of heat shock, indicating that HSP-70 is not essential to the heat stress-induced protective effect reported in this study.

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Section: Discussionsupporting

confidence: 93%

Heat Shock–Induced Protection of Renal Proximal Tubular Epithelial Cells from Cold Storage and Rewarming Injury

Healy¹,

Daly²,

Docherty³

et al. 2006

Journal of the American Society of Nephrology

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“…GA also activates p70s6k, a key factor in mTOR signaling pathway, which results in long-term memory improvement, disrupted by exogenous Aβ. P70s6k activation also reduces neuronal apoptosis by activation of autophagy, reduction of oxidative stress and the activation of antiapoptotic agents, such as Bcl-2 the protective role of Hsp90 against neuronal apoptosis also has been reported in a cellular model of Huntington disease (Lee et al 2001). Our data suggest that Hsp70 upregulation following GA-mediated Hsp90 inhibition not only elevated intracellular antioxidant level, but also reduced significantly apoptotic markers.…”

Section: Discussionsupporting

confidence: 75%

Collaboration of geldanamycin-activated P70S6K and Hsp70 against beta-amyloid-induced hippocampal apoptosis: an approach to long-term memory and learning

Zare

Motamedi

Digaleh

et al. 2015

Cell Stress and Chaperones

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One of the neuropathological hallmarks of Alzheimer's disease (AD) is the accumulation of betaamyloid peptides (Aβ) in senile plaques. Aβ-induced oxidative stress is believed to be responsible for degeneration and apoptosis of neurons and consequent cognitive and memory deficits. Here, we investigated the possible neuroprotective effect of the heat shock protein 90 (Hsp90) inhibitor geldanamycin (GA) against amyloid pathogenesis in adult male Wistar rats. GA or vehicle was injected into the lateral cerebral ventricles of rats 24 h before injection of Aβ (1-42) in CA1 area of hippocampus. The learning and memory of the rats were assessed 7 days after injection of Aβ using passive avoidance (PA) task. As potential contributing factors in Aβ-induced memory decline, we evaluated apoptotic markers and also used terminal-transferase UTP nick end labeling (TUNEL) technique to detect apoptosis in the hippocampus of Aβ-injected rats. Our behavioral data suggest that GA pretreatment can significantly suppress memory deficits in Aβ-injected rats. There was also not only a marked increase in Hsp70 level but also upregulated 70 kDa ribosomal protein S6 kinase (p70S6K) in the hippocampus of GA-treated groups with a reduction in apoptotic factors including caspase-3, poly (ADP-ribose) polymerase, Bax/Bcl-2 ratio, and TUNELpositive cells as well. Thus, we conclude that GA exerts its protective effects against Aβ (1-42) toxicity and memory deficits, at least in part, by upregulating of Hsp70 and P70S6K.

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“…One notion derived from the conflicting role of HSP70 or HSP90 in apoptosis (Galea-Lauri et al, 1996;Meriin et al, 1998;Robertson et al, 1999;Wagstaff et al, 1999;Lee et al, 2001;Lopez-Maderuelo et al, 2001) is that whether an HSP family member is pro-or antiapoptotic depends on the cell type or the stressor. The present study provided credence to this notion by demonstrating a differential neuroprotective role for HSP70 and HSP90 in the RVLM against fatal endotoxemia.…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, the best-studied cellular action of HSPs by far is protection against apoptosis, based primarily on studies using cell lines under nonpathological conditions. Within the HSP family, HSP70 and HSP90 are two members that are often reported to be antiapoptotic (Meriin et al, 1998;Robertson et al, 1999;Lee et al, 2001).…”

mentioning

confidence: 99%

In the Rostral Ventrolateral Medulla, the 70-kDa Heat Shock Protein (HSP70), but Not HSP90, Confers Neuroprotection against Fatal Endotoxemia via Augmentation of Nitric-Oxide Synthase I (NOS I)/Protein Kinase G Signaling Pathway and Inhibition of NOS II/Peroxynitrite Cascade

Li¹,

Chan²,

Chan³

et al. 2005

Mol Pharmacol

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Heat shock proteins (HSPs) represent a group of highly conserved intracellular proteins that participate in protective adaptation against cellular stress. We evaluated the neuroprotective role of the 70-kDa HSP (HSP70) and the 90-kDa HSP (HSP90) at the rostral ventrolateral medulla (RVLM), the medullary origin of sympathetic vasomotor tone, during fatal endotoxemia. In Sprague-Dawley rats maintained under propofol anesthesia, Escherichia coli lipopolysaccharide (30 mg/kg, i.v.) induced a decrease (phase I), followed by an increase (phase II; "pro-life" phase) and a secondary decrease (phase III; "pro-death" phase) in the power density of the vasomotor component of systemic arterial pressure spectrum, along with progressive hypotension or bradycardia. Proteomic and Western blot analyses revealed that whereas HSP70 expression in the RVLM was significantly augmented during phases I and II and returned to baseline during phase III endotoxemia, HSP90 protein expression remained constant. The increase in HSP70 level was significantly blunted on pretreatment with microinjection of the transcription inhibitor actinomycin D or protein synthesis inhibitor cycloheximide into the bilateral RVLM. Functional blockade of HSP70 in the RVLM by an anti-HSP70 antiserum or prevention of synthesis by an antisense hsp70 oligonucleotide exacerbated mortality or potentiated the cardiovascular depression during experimental endotoxemia, alongside significantly reduced nitric-oxide synthase (NOS) I or protein kinase G (PKG) level or augmented NOS II or peroxynitrite level in the RVLM. We conclude that whereas HSP90 is ineffective, de novo synthesis of HSP70 in the RVLM may confer neuroprotection during fatal endotoxemia by preventing cardiovascular depression via enhancing the sympathoexcitatory NOS I/PKG signaling pathway and inhibiting the sympathoinhibitory NOS II/peroxynitrite cascade in the RVLM.The heat shock proteins (HSPs) represent a group of intracellular proteins that are highly conserved across species and are thought to participate in protective adaptation that spares cells from otherwise lethal consequences of exposure to heat, toxins, infection, seizure, trauma, ischemia, or other cellular stresses (Lindquist and Craig, 1988;Welch, 1992;Morimoto and Santoro, 1998). Because of their critical roles in intracellular processing, synthesis, transportation, and degradation of proteins, HSPs have been termed molecular chaperones. The cellular protective mechanisms of HSPs are believed to be related to these chaperone functions, which lead to the prevention of protein denaturation and promotion of refolding of damaged proteins after stress. In addition, HSP chaperones may sustain proteins in the productive folding pathway or maintain newly synthesized proteins in an unfolded conformation suitable for translocation across membranes (Welch, 1992;Morimoto and Santoro, 1998). Article, publication date, and citation information can be found at http://molpharm.aspetjournals.org. doi:10.1124/mol.105.011684. ABBREVIATIONS:HSP, hea...

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The Protective Role of HSP90 against 3-Hydroxykynurenine-Induced Neuronal Apoptosis

Cited by 52 publications

References 24 publications

Heat Shock–Induced Protection of Renal Proximal Tubular Epithelial Cells from Cold Storage and Rewarming Injury

Heat Shock–Induced Protection of Renal Proximal Tubular Epithelial Cells from Cold Storage and Rewarming Injury

Collaboration of geldanamycin-activated P70S6K and Hsp70 against beta-amyloid-induced hippocampal apoptosis: an approach to long-term memory and learning

In the Rostral Ventrolateral Medulla, the 70-kDa Heat Shock Protein (HSP70), but Not HSP90, Confers Neuroprotection against Fatal Endotoxemia via Augmentation of Nitric-Oxide Synthase I (NOS I)/Protein Kinase G Signaling Pathway and Inhibition of NOS II/Peroxynitrite Cascade

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