A non-toxic heat shock protein 70 inducer, geranylgeranylacetone, suppresses apoptosis of cultured rat hepatocytes caused by hydrogen peroxide and ethanol

Ikeyama, Shizuo; Kusumoto, Kenji; Miyake, Hidenori; Rokutan, Kazuhito; Tashiro, Seiki

doi:10.1016/s0168-8278(01)00053-8

Cited by 82 publications

(65 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…4), suggesting that GGA pretreatment attenuates lightinduced retinal damage morphologically and functionally. The anti-apoptotic effects of GGA were previously reported in the ethanol-and H 2 O 2 -induced cultured rat hepatocyte injury (Mizushima et al, 1999) and in the ethanol-induced cultured guinea pig gastric mucosal cell injury (Ikeyama et al, 2001). The present study showed the anti-apoptotic effects of GGA in a model of light-induced photoreceptor cell damage.…”

Section: Discussionmentioning

confidence: 64%

Cytoprotective Effects of Geranylgeranylacetone against Retinal Photooxidative Damage

Tanito¹,

Kwon²,

Kondo³

et al. 2005

J. Neurosci.

View full text Add to dashboard Cite

Exposure to excessive light induces retinal photoreceptor cell damage, leading to development and progression of various retinal diseases. We tested the effect of geranylgeranylacetone (GGA), an acyclic polyisoprenoid, on light-induced retinal damage in mice. Oral treatment with GGA (1.0 mg/d) for 5 d induced thioredoxin (Trx) and heat shock protein 72 (Hsp72) predominantly in the retinal pigment epithelium (RPE). After white light exposure (8000 lux for 2 h), the percentage of terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling-positive photoreceptor cells decreased significantly at 24 and 96 h, and the number of photoreceptor cell nuclei at 96 h and the electroretinographic amplitudes of the a- and b-waves at 4 and 10 d increased significantly in GGA-pretreated mice compared with saline-pretreated mice. Light-induced upregulations of 8-hydroxy-2-deoxyguanosine and 4-hydroxy-2-nonenal-modified protein, markers of oxidative stress, were inhibited by GGA pretreatment. To elucidate the cytoprotective mechanism of GGA and Trx, we used human K-1034 RPE cells and mouse photoreceptor-derived 661W cells. In K-1034 cells, GGA (10 μm) induced intracellular Trx, Hsp72, and extracellular Trx but not extracellular Hsp72. Extracellular Trx (0.75 nm) attenuated H2O2(200 μm)-induced cell damage in 661W cells. Pretreatment with GGA and overexpression of Trx in K-1034 cells counteracted H2O2(50 μm)-induced attenuation of cellular latex bead incorporation. Protection of phagocytotic activity through induction of Trx and possibly Hsp72 in RPE cells and elimination of oxidative stress in the photoreceptor layer through release of Trx from RPE cells may be mechanisms of GGA-mediated cytoprotection. Therefore, Trx is a neurotrophic factor released from RPE cells and plays a crucial role in maintaining photoreceptor cell integrity.

show abstract

Section: Discussionmentioning

confidence: 64%

Cytoprotective Effects of Geranylgeranylacetone against Retinal Photooxidative Damage

Tanito¹,

Kwon²,

Kondo³

et al. 2005

J. Neurosci.

View full text Add to dashboard Cite

show abstract

“…GGA was reported to specifically induce transcriptional activation of HSF1 and expression of HSP72 mRNA in cultured guinea pig gastric mucosal cells 17 and to exert priming effects for enhanced HSP72 induction. 20 It has been reported that protein kinase C mediates the phosphorylation of HSF1, resulting in HSP72 expression in cultured human epidermoid A431 cells. Oral administration of GGA activates protein kinase C, leading to the phosphorylation and translation of HSF1, and thus promotes the expression of HSP72 protein.…”

Section: Discussionmentioning

confidence: 99%

Potential Role for Heat Shock Protein 72 in Antagonizing Cerebral Vasospasm After Rat Subarachnoid Hemorrhage

et al. 2004

View full text Add to dashboard Cite

Background-Cerebral vasospasm can be defined as delayed-onset narrowing of the cerebral arteries that can occur after a spontaneous aneurysmal subarachnoid hemorrhage (SAH). Despite a large number of experimental and clinical investigations, the exact pathophysiology of vasospasm remains unknown. Using a fluorescence differential-display system, we have identified the gene encoding heat shock protein 72 (HSP72) as being highly upregulated by cerebral vasospasm. We therefore elucidated the role of the HSP72 gene in cerebral vasospasm in a rat experimental SAH model. Methods and Results-By angiography, cerebral vasospasm was detected from day 1, with maximal narrowing detected on day 2. Intracisternal injection of antisense HSP72 oligodeoxynucleotide led to specific inhibition of HSP72 gene expression and significantly aggravated cerebral vasospasm on days 2 and 3 of the angiographic studies. Oral administration of geranylgeranylacetone (GGA), an antiulcer drug, enhanced HSP72 induction and reduced cerebral vasospasm. Conclusions-These results suggest HSP72 plays a novel role in antagonizing delayed cerebral vasospasm after SAH and that GGA provides protective effects against delayed cerebral vasospasm, at least partly via induction of HSP72.

show abstract

“…Hsp70 protects cells from various stresses, including apoptosisinducing stresses and agents, such as oxidative stress, nitric oxide, tumor necrosis factor, anticancer drugs, ceramide, and radiation (Samali and Orrenius 1998). In hepatocytes, Hsp70 was reported to protect cells from tumor necrosis factor-␣, prostaglandin, hydrogen peroxide, ethanol, or ultraviolet C (Kim et al 1997;Ahn et al 1998;Chen et al 1999;Ikeyama et al 2001). Although antiapoptotic effects of Hsp70 have been repeatedly reported, related mechanisms are unclear.…”

Section: Discussionmentioning

confidence: 99%

Induction of molecular chaperones in carbon tetrachloride–treated rat liver: implications in protection against liver damage

Kwang-Jong¹,

Terada²,

Oyadomari³

et al. 2004

Cell Stress Chaperones

View full text Add to dashboard Cite

Carbon tetrachloride (CCl 4 ) induces liver damage, apparently through the formation of free-radical metabolites. Molecular chaperones such as heat shock protein (Hsp) of 70 kDa have been found to protect cells from various stresses. We previously found that cytosolic chaperone pairs of the Hsp70 family and their DnaJ homolog cochaperones prevent nitric oxide-mediated apoptosis and heat-induced cell death. Expression of cytosolic chaperones, including Hsp70; heat shock cognate (Hsc) 70; and DnaJ homologs dj1 (DjB1/Hsp40/hdj-1), dj2 (DjA1/HSDJ/hdj-2), dj3 (DjA2), and dj4 (DjA4), in the liver of CCl 4 -treated rats was analyzed. Messenger ribonucleic acids for all these chaperones were markedly induced 3-12 hours after CCl 4 treatment with a maximum at 6 hours. Hsp70 and dj1 proteins were markedly induced at 6-24 hours with a maximum at 12 hours, whereas dj2 and dj4 were moderately induced at around 12 hours. Hsc70 was weakly induced after treatment, and dj3 was little induced. To better understand the significance of the induction of chaperones, the effect of preinduction of chaperones on CCl 4 -induced liver damage was analyzed. When chaperones were preinduced in the liver by heat treatment, increase in serum alanine aminotransferase activity after CCl 4 treatment was significantly attenuated. Hsp90, another major cytosolic chaperone, also was induced by heat treatment. On the other hand, Mn-and Cu/Zn-superoxide dismutase were not induced by heat treatment or by CCl 4 treatment. These results suggest that cytosolic chaperones of Hsp70 and DnaJ families or Hsp90 (or both) are induced in CCl 4 -treated rat liver to protect the hepatocytes from the damage being inflicted.

show abstract

A non-toxic heat shock protein 70 inducer, geranylgeranylacetone, suppresses apoptosis of cultured rat hepatocytes caused by hydrogen peroxide and ethanol

Cited by 82 publications

References 39 publications

Cytoprotective Effects of Geranylgeranylacetone against Retinal Photooxidative Damage

Cytoprotective Effects of Geranylgeranylacetone against Retinal Photooxidative Damage

Potential Role for Heat Shock Protein 72 in Antagonizing Cerebral Vasospasm After Rat Subarachnoid Hemorrhage

Induction of molecular chaperones in carbon tetrachloride–treated rat liver: implications in protection against liver damage

Contact Info

Product

Resources

About