Pharmacologic preconditioning effects: prostaglandin E1 induces heat-shock proteins immediately after ischemia/reperfusion of the mouse liver.
Prostaglandin E1 (PGE1) has several potential therapeutic effects, including cytoprotection, vasodilation, and inhibition of platelet aggregation. This study investigates the protective action of PGE1 against hepatic ischemia/reperfusion injury in vivo using a complementary DNA microarray. PGE1 or saline was continuously administered intravenously to mice in which the left lobe of the liver was made ischemic for 30 minutes and then reperfused. Livers were harvested 0, 10, and 30 minutes postreperfusion. Messenger RNA was extracted, and the samples were labeled with two different fluorescent dyes and hybridized to the RIKEN set of 18,816 full-length enriched mouse complementary DNA microarrays. Serum alanine aminotransferase and aspartate aminotransferase levels at 180 minutes postreperfusion were significantly lower in the PGE1-treated group than in the saline-treated group. The cDNA microarray analysis revealed that the genes encoding heat-shock protein (HSP) 70, glucose-regulated protein 78, HSP86, and glutathione S-transferase were upregulated at the end of the ischemic period (0 minutes postreperfusion) in the PGE1 group. Our results suggested that PGE1 induces HSPs immediately after ischemia reperfusion. HSPs might therefore play an important role in the protective effects of PGE1 against ischemia/reperfusion injury of the liver.
Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan. k-matsuo@kf6.so-net.ne.jp
Ken-ichi
K
Matsuo
Shinji
S
Togo
Hitoshi
H
Sekido
Tomoyuki
T
Morita
Masako
M
Kamiyama
Daisuke
D
Morioka
Toru
T
Kubota
Yasuhiko
Y
Miura
Kuniya
K
Tanaka
Takashi
T
Ishikawa
Yasushi
Y
Ichikawa
Itaru
I
Endo
Hitoshi
H
Goto
Hiroyuki
H
Nitanda
Yasushi
Y
Okazaki
Yoshihide
Y
Hayashizaki
Hiroshi
H
Shimada
D000527:Alprostadil / Q000494:pharmacology*; D000818:Animals; D016000:Cluster Analysis; D018076:DNA, Complementary / Q000032:analysis; D004195:Disease Models, Animal; D006360:Heat-Shock Proteins / Q000187:drug effects* / Q000502:physiology; D007262:Infusions, Intravenous; D007511:Ischemia / Q000628:therapy*; D019194:Ischemic Preconditioning / Q000379:methods*; D008099:Liver / Q000098:blood supply*; D008106:Liver Cirrhosis, Experimental; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011336:Probability; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000517:prevention & control; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012680:Sensitivity and Specificity
D018076:DNA, Complementary; D006360:Heat-Shock Proteins; D000527:Alprostadil