Heat shock protein 70 or heat shock protein 27 overexpressed in human endothelial cells during posthypoxic reoxygenation can protect from delayed apoptosis

Kabakov, Alexander E.; Budagova, Karina R.; Bryantsev, Anton L.; Latchman, David S.

doi:10.1379/1466-1268(2003)008<0335:hspohs>2.0.co;2

Cited by 52 publications

(49 citation statements)

References 30 publications

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“…Both effects were attributed to the ability of STAT1 to activate expression of either proapoptotic (Kumar et al, 1997;Stephanou et al, 2000Stephanou et al, , 2001 or prosurvival proteins (Stephanou et al, 1999;Madamanchi et al, 2001;Terui et al, 2004). We found here that in WT cells serine-phosphorylated STAT1 promotes cell survival through the regulation of expression of two known prosurvival genes, MCL-1 and HSP27 (Kabakov et al, 2003;Michels et al, 2005).…”

Section: Stat1 Is a Prosurvival Factor In Wilms' Tumorsupporting

confidence: 52%

Serine-phosphorylated STAT1 is a prosurvival factor in Wilms' tumor pathogenesis

et al. 2006

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Wilms' tumor (WT), one of the most common pediatric solid cancers, arises in the developing kidney as a result of genetic and epigenetic changes that lead to the abnormal proliferation and differentiation of the metanephric blastema. As activation of signal transducers and activators of transcription (STATs) plays an important role in the maintenance/growth and differentiation of the metanephric blastema, and constitutively activated STATs facilitate neoplastic behaviors of a variety of cancers, we hypothesized that dysregulation of STAT signaling may also contribute to WT pathogenesis. Accordingly, we evaluated STAT phosphorylation patterns in tumors and found that STAT1 was constitutively phosphorylated on serine 727 (S727) in 19 of 21 primary WT samples and two WT cell lines. An inactivating mutation of S727 to alanine reduced colony formation of WT cells in soft agar by more than 80% and induced apoptosis under conditions of growth stress. S727-phosphorylated STAT1 provided apoptotic resistance for WT cells via upregulation of expression of the heat-shock protein (HSP)27 and antiapoptotic protein myeloid cell leukemia (MCL)-1. The kinase responsible for STAT1 S727 phosphorylation in WT cells was identified based upon the use of selective inhibitors as protein kinase CK2, not p38, MAP-kinase kinase (MEK)1/2, phosphatidylinositol 3 0 -kinase, protein kinase C or Ca/calmodulindependent protein kinase II (CaMKII). The inhibition of CK2 blocked the anchorage-independent growth of WT cells and induced apoptosis under conditions of growth stress. Our findings suggest that serine-phosphorylated STAT1, as a downstream target of protein kinase CK2, plays a critical role in the pathogenesis of WT and possibly other neoplasms with similar STAT1 phosphorylation patterns.

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Section: Stat1 Is a Prosurvival Factor In Wilms' Tumorsupporting

confidence: 52%

Serine-phosphorylated STAT1 is a prosurvival factor in Wilms' tumor pathogenesis

et al. 2006

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“…Disease Implications-It has been shown that the increases in Hsp levels are critical for cell survival during hypoxia and the subsequent reoxygenation (29,38). Our results indicate that it is through the HIF-1 pathway that the cell achieves this Hsp increase and is a means to protect against the stress of hypoxia.…”

Section: Complex Regulation Of Physiological Response Pathways-mentioning

confidence: 60%

“…Full Induction of Hsps and Viability during Reoxygenation Is Dependent on Increased Hsf Levels-During the return to normal oxygen conditions, Hsp levels remain high and are critical to tissue survival during this reoxygenation (28,29). The effect of the HIF-1-dependent increase in Hsf level on Hsp expression persists during reoxygenation.…”

Section: Full Induction Of Hsps During Hypoxia Is Dependent On Hif-1␣mentioning

confidence: 99%

Induction of the Heat Shock Pathway during Hypoxia Requires Regulation of Heat Shock Factor by Hypoxia-inducible Factor-1

Baird

Turnbull

Johnson

2006

Journal of Biological Chemistry

144

100

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Activation of heat shock proteins (Hsps) is critical to adaptation to low oxygen levels (hypoxia) and for enduring the oxidative stress of reoxygenation. Hsps are known to be regulated by heat shock factor (Hsf), but our results demonstrate an unexpected regulatory link between the oxygen-sensing and heat shock pathways. Hsf transcription is up-regulated during hypoxia due to direct binding by hypoxia-inducible factor-1 (HIF-1) to HIF-1 response elements in an Hsf intron. This increase in Hsf transcripts is necessary for full Hsp induction during hypoxia and reoxygenation. The HIF-1-dependent increase in Hsps has a functional impact, as reduced production of Hsps decreases viability of adult flies exposed to hypoxia and reoxygenation. Thus, HIF-1 control of Hsf transcriptional levels is a regulatory mechanism for sensitizing heat shock pathway activity in order to maximize production of protective Hsps. This cross-regulation represents a mechanism by which the low oxygen response pathway has assimilated complex new functions by regulating the key transcriptional activator of the heat shock pathway.In order to endure oxygen deprivation, most eukaryotes utilize a conserved set of cellular adaptations (1). Many of these changes are brought about by the activation of the transcription factor hypoxia-inducible factor-1 (HIF-1), 2 a heterodimeric complex composed of HIF-1␣ and HIF-1␤ subunits. When this complex is formed it binds to specific DNA enhancer sequences and regulates the activity of target genes. Both HIF-1␣ and HIF-1␤ are constitutively expressed in normal oxygen conditions (normoxia), but HIF-1␣ protein is quickly degraded before dimerization can occur with HIF-1␤ (2). Normoxic HIF-1␣ degradation is mediated by a series of hydroxylations and ubiquitinations that tag HIF-1␣ for disposal through the proteasome (3-6).The HIF-1 complex transcriptionally regulates a wide array of genes involved in anaerobic metabolism, growth, proliferation, angiogenesis, and cell death (7,8). This multifaceted control of cellular and organismal physiological pathways is exploited by solid tumors through the natural hypoxic environment caused by rapid growth or genetic alterations that stabilize HIF-1␣ (9). Overexpression or activation of HIF-1␣ is often seen in a wide array of cancers and is correlated with patient survival (10), and studies have shown that targeting the HIF-1 pathway is a promising means of cancer therapy (11,12). Thus, HIF-1 is a central regulator of normal and pathological changes in response to low oxygen.Although many genes that are up-regulated during hypoxia are known to be regulated by HIF-1, there are also diverse sets of genes up-regulated that have not been linked to the actions of HIF-1. Among these are the highly conserved heat shock proteins (Hsps) that are highly up-regulated during hypoxia but have not been linked to HIF-1 regulation (13). Hsps are known to act as cellular chaperones for proteins that are misfolded by cellular stresses (14). Heat shock factor (Hsf) was one of the first studied...

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“…31 Alternatively, the anti-apoptotic and protective roles of HSP27 reported by several studies in the ischemiareperfusion injury showing the active adaptive changes following kidney transplantation. [33][34][35] …”

Section: Hsp27 Response To Stress Conditions In Kidney Diseasementioning

confidence: 99%

Heat Shock Protein 27(HSP27) in Kidney Disease: Potentials for Diagnosis and Therapy

Mahgoub

2017

Journal of Advanced Pharmacy Research

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Heat shock protein 70 or heat shock protein 27 overexpressed in human endothelial cells during posthypoxic reoxygenation can protect from delayed apoptosis

Cited by 52 publications

References 30 publications

Serine-phosphorylated STAT1 is a prosurvival factor in Wilms' tumor pathogenesis

Serine-phosphorylated STAT1 is a prosurvival factor in Wilms' tumor pathogenesis

Induction of the Heat Shock Pathway during Hypoxia Requires Regulation of Heat Shock Factor by Hypoxia-inducible Factor-1

Heat Shock Protein 27(HSP27) in Kidney Disease: Potentials for Diagnosis and Therapy

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