Original ArticlesEffects of geranyl-geranyl-acetone administration before heat shock preconditioning for conferring tolerance against ischemia-reperfusion injury in rat livers☆,☆☆
Section snippets
Animals
This study was conducted in accordance with the Animal Protection Guidelines of Kyoto University. Two hundred male Wistar rats (Shizuoka Laboratory Animal Center, Hamamatsu, Japan) weighing between 230 and 260 g (10-11 weeks of age) were used. They were housed in chip-bedded cages in an air-conditioned room (24°C ± 1°C) with controlled 12-hour light/dark cycles. Rats were permitted free access to water and standard rat chow.
Administration of GGA
After overnight fasting, each rat in the GGA groups was given 8 mL/kg
Detection of HSP72
Fig 2, A , shows the production of HSP72 in liver tissue 48 hours after heat shock exposure in liver tissue in all groups.
Discussion
There are two ways to reduce the heat shock stress necessary to induce HSP72: one is to shorten the duration of exposure, and the other is to decrease the temperature. The present study demonstrated that the administration of GGA before heat shock increases the responsiveness of hepatocytes to heat shock stress. Neither an administration of GGA alone nor a 5-minute heat shock at 42°C was enough to trigger a stress response or to induce detectable levels of HSP72 in hepatocytes. After
Acknowledgements
We thank Eisai Co, Ltd, for the generous gift of GGA and Dr Koji Uchida (Laboratory of Food and Biodynamics, Nagoya University School of Agriculture, Nagoya, Japan) for providing polyclonal antibody against HNE-modified proteins.
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2015, Pulmonary Pharmacology and TherapeuticsCitation Excerpt :Many studies have revealed that accumulated reactive oxygen species (ROS) and activated inflammatory reaction played important role in the pathology of lung IRI [2,6,7], but the specific prevention for lung IRI is not available yet. Geranylgeranylacetone (GGA), an efficient HSP70 inducer, is currently only used as an oral anti-ulcer medication mainly in China and Japan, but accumulating studies indicated that GGA could protect organs against IRI, such as kidney IRI [8], myocardial IRI [9] and liver IRI [10,11] by inducing heat shock protein 70 (HSP70). A study of Sugawara et al. observed the effect of GGA against ischemia-reperfusion injury after lung transplantation [12], but the mechanism was not investigated.
Geranylgeranylacetone protects against cerebral ischemia and reperfusion injury: HSP90 and eNOS phosphorylation involved
2015, Brain ResearchCitation Excerpt :Geranylgeranylacetone (GGA) is an acyclic polyisoprenoid used as an oral anti-ulcer medication. Recently many studies have found out that, by inducing heat shock proteins(HSPs), GGA is protective against various I/R injury, including myocardial I/R injury(Yamanaka et al., 2003), acute kidney I/R injury (Kim et al., 2014), liver ischemia–reperfusion injury (Fan et al., 2005; Yamagami et al., 2000). The role of HSP70 was intensely investigated in these studies, but the role of HSP90, another HSP induced by GGA, was seldom studied.
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Supported in part by grants from the Scientific Research Fund of the Ministry of Education, Japan (grants 09307026 and 10557120) and in part by The Japan Society for the Promotion of Science, Japan (grant JSPS-RFTF 96I00204).
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Reprint requests: Yuzo Yamamoto, MD, Department of Gastroenterological Surgery, Kyoto University, Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.