Geranylgeranylacetone protects against cerebral ischemia and reperfusion injury: HSP90 and eNOS phosphorylation involved

He, Dake; Song, Xiu–Peng; Li, Ling

doi:10.1016/j.brainres.2014.12.019

Cited by 13 publications

(9 citation statements)

References 36 publications

(38 reference statements)

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“…In multiple animal models of ischemia and reperfusion, GGA prevents oxidative stress in the liver, heart, brain, kidney, and retina (Ohkawara et al, 2006; Tanito et al, 2005; Suzuki et al, 2005; Zhao et al, 2013; He et al, 2015). GGA's cytoprotective effect was associated primarily with induction of HSP70, as well as stimulation of the thioredoxin system (Patury et al, 2009; Hirota et al, 2002).…”

Section: Hsp70 and Rgc Survivalmentioning

confidence: 99%

Heat shock proteins in the retina: Focus on HSP70 and alpha crystallins in ganglion cell survival

Piri

Kwong

et al. 2016

Progress in Retinal and Eye Research

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Heat shock proteins (HSPs) belong to a superfamily of stress proteins that are critical constituents of a complex defense mechanism that enhances cell survival under adverse environmental conditions. Cell protective roles of HSPs are related to their chaperone functions, antiapoptotic and antinecrotic effects. HSPs' antiapoptotic and cytoprotective characteristics, their ability to protect cells from a variety of stressful stimuli, and the possibility of their pharmacological induction in cells under pathological stress make these proteins an attractive therapeutic target for various neurodegenerative diseases; these include Alzheimer's, Parkinson's, Huntington's, prion disease, and others. This review discusses the possible roles of HSPs, particularly HSP70 and small HSPs (alpha A and alpha B crystallins) in enhancing the survival of retinal ganglion cells (RGCs) in optic neuropathies such as glaucoma, which is characterized by progressive loss of vision caused by degeneration of RGCs and their axons in the optic nerve. Studies in animal models of RGC degeneration induced by ocular hypertension, optic nerve crush and axotomy show that upregulation of HSP70 expression by hyperthermia, zinc, geranyl-geranyl acetone, 17-AAG (a HSP90 inhibitor), or through transfection of retinal cells with AAV2-HSP70 effectively supports the survival of injured RGCs. RGCs survival was also stimulated by overexpression of alpha A and alpha B crystallins. These findings provide support for translating the HSP70- and alpha crystallin-based cell survival strategy into therapy to protect and rescue injured RGCs from degeneration associated with glaucomatous and other optic neuropathies.

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Section: Hsp70 and Rgc Survivalmentioning

confidence: 99%

Heat shock proteins in the retina: Focus on HSP70 and alpha crystallins in ganglion cell survival

Piri

Kwong

et al. 2016

Progress in Retinal and Eye Research

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“…Various studies indicate that Hsp-70 mediates anti-inflammatory effects and decreases inflammatory cytokine production. For example, increased levels of Hsp-70 are detected in cerebral IRI [29, 30]. Neuroprotective effects are described for Hsp-90 as well [31, 32].…”

Section: Discussionmentioning

confidence: 99%

The Carbon monoxide releasing molecule ALF-186 mediates anti-inflammatory and neuroprotective effects via the soluble guanylate cyclase ß1 in rats’ retinal ganglion cells after ischemia and reperfusion injury

Ulbrich

Hagmann

Buerkle

et al. 2017

J Neuroinflammation

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BackgroundThe endogenously produced gaseous molecule carbon monoxide is able to promote organ protection after ischemia-reperfusion injuries (IRI). The impact of carbon monoxide releasing molecules (CORM) regarding inflammation in neuronal tissues has not been studied in detail. In this investigation, we aimed to analyze the effects of the CORM ALF-186 on neuro-inflammation and hypothesized that the soluble guanylate cyclase (sGC) is playing a decisive role.MethodsRetinal ischemia-reperfusion injury was performed for 60 min in Sprague-Dawley rats. Thereafter, the CORM ALF-186 (10 mg/kg) in the presence or absence of the sGC inhibitor ODQ was injected via a tail vein. Retinal tissue was harvested 24 h later to analyze mRNA or protein expression of sGC-β1 subunit, transcription factors NF-κB and CREB, the inflammatory cytokines TNF-α and IL-6, as well as the heat shock proteins (HSP) HSP-70 and HSP-90. Immunohistochemistry was performed on frozen sections of the retina. The overall neuroprotective effect of ALF-186 was assessed by counting fluorogold-pre-labeled retinal ganglion cells (RGC) 7 days after IRI.ResultsIschemia-reperfusion mediated loss of vital RGC was attenuated by the administration of ALF-186 after injury. ALF-186 treatment after IRI induced sGC-ß1 leading to a decreased NF-κB and CREB phosphorylation. Consecutively, ALF-186 mitigated IRI induced TNF-α and IL-6 expression in the retina and in the rats’ serum. Moreover, ALF-186 attenuated heat shock protein 70 (Hsp-70) while increasing Hsp-90. The sGC-inhibitor ODQ attenuated the anti-inflammatory effects of ALF-186 and increased retinal loss of ganglion cells. These results were confirmed by immunohistochemistry.ConclusionThe CORM ALF-186 protected RGC from IRI induced loss. Furthermore, ALF-186 reduced IRI mediated neuroinflammation in the retina and in the serum by activating sGC. Inhibition of sGC stopped the beneficial and protective effects of ALF-186. ALF-186 may present a promising therapeutic alternative in treating inflammation after neuronal IRI.

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“…A number of studies have reported pathophysiological roles of HSP90 in various diseases, including bacterial and viral infection [108][109][110][111], autoimmune diseases [112][113][114][115][116], cerebrovascular diseases [117][118][119], and cancer. It is worth noting that the up-regulation of HSP90 in cancer is due to the fact that cancer cells are constantly under stressful conditions such as acidosis, hypoxia, metabolic, and nutrient deficiency [4,15,120].…”

Section: Cdc37 Is a Key Co-chaperone For Hsp90 In Cancer Progression mentioning

confidence: 99%

Roles of Extracellular Vesicles (EVs) Carrying HSPs in Cancer Biomarkers, Immune Surveillance, and Immune Evasion

Taha¹,

Ono²,

Eguchi³

2019

Preprint

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Extracellular vesicles (EV) released by tumor cells are a major aspect of the resistance-associated secretory phenotype (RASP), by which immune evasion can be established. Heat shock proteins (HSPs) are an evolutionarily conserved family of molecular chaperones, which stabilize proteins, minimize protein misfolding and aggregation within the cell, besides facilitating protein translocation, refolding and degradation. (i) Releases of extracellular HSPs (ex-HSP) and EV-associated HSPs (EV-HSP) are essential in RASP, by which molecular cotransfer of HSPs with oncogenic factors into recipient cells can promote cancer progression and resistance against stress such as hypoxia, radiation, chemicals, and immune system. (ii) RASP of tumor cells can eject anticancer drugs, molecularly targeted therapeutics, and immune checkpoint inhibitors with EVs. (iii) Cytotoxic lipids can be also released from tumor cells as RASP. Nevertheless, ex-HSP and EV-HSP can play immunostimulatory and immunosuppressive roles by binding to receptors such as LRP1/CD91/A2MR, scavenger receptors, and toll-like receptors expressed on recipient cells. Liquid biopsy of HSPs in body fluids may be useful in diagnosis, prognosis, and treatment in cancer. Regarding HSP90-targeted therapeutics, we summarize the pros, cons, and problem solutions in this review. Although production of HSPs are canonically induced by heat shock factor 1 (HSF1) and hypoxia-inducible factor 1 (HIF-1), recent studies discovered that production of HSPs is also regulated by matrix metalloproteinase 3 (MMP3) and heterochromatin protein 1 (HP1) and production of cochaperone CDC37 is reciprocally regulated by myeloid zinc finger 1 (MZF1) and SCAN-D1.

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Geranylgeranylacetone protects against cerebral ischemia and reperfusion injury: HSP90 and eNOS phosphorylation involved

Cited by 13 publications

References 36 publications

Heat shock proteins in the retina: Focus on HSP70 and alpha crystallins in ganglion cell survival

Heat shock proteins in the retina: Focus on HSP70 and alpha crystallins in ganglion cell survival

The Carbon monoxide releasing molecule ALF-186 mediates anti-inflammatory and neuroprotective effects via the soluble guanylate cyclase ß1 in rats’ retinal ganglion cells after ischemia and reperfusion injury

Roles of Extracellular Vesicles (EVs) Carrying HSPs in Cancer Biomarkers, Immune Surveillance, and Immune Evasion

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