Figure 4

Inhibition of pertussis toxin-sensitive G-proteins, ERK MAPK, or Akt but not eNOS prevents hepatic (a, ALT) and renal (b, creatinine) protection by sphinganine-1-phosphate in C57BL/6 mice subjected to 60 min liver ischemia and 24 h reperfusion. Mice were pretreated with PD98059 (PD, an inhibitor of MEK1 to inhibit ERK phosphorylation, 1 mg/kg, i.p., N=6), with wortmannin (Wort, an inhibitor of PI3K to inhibit Akt phosphorylation, 1 mg/kg, i.p., N=6) or with N-iminoethyl-L-ornithine (L-NIO, a selective inhibitor of eNOS, 10 mg/kg i.p. N=6) 20 min before vehicle or sphinganine-1-phosphate treatment. Some mice were pretreated with pertussis toxin (PTX, 25 μg/kg, i.p.) 48 h before sphinganine-1-phosphate treatment. Sphinganine-1-phosphate was administered 0.1 mg/kg i.v. immediately before reperfusion and 0.2 mg/kg s.c. 2 h after reperfusion. Data are presented as means±s.e.m. ^*P<0.05 vs vehicle-treated IR group. ^#P<0.05 vs vehicle-treated sphinganine-1-phosphate-treated hepatic IR group.