Figure 7.

Activation of p38 is involved in malonate-induced cell death. Rats were administered intrastriatally with malonate (1.5 μmol/2 μL) alone or in combination with the p38 inhibitor, SB203580 (1 nmol/2 μL). (A) Representative cytochrome oxidase-stained slices and quantification of malonate-induced striatal lesions (mm³) showing that SB203580 significantly inhibited the neurotoxic effect of malonate 72 h after treatment. Data are mean ± SEM (n = 6) [t₍₁₁₎ = 12.89, P < 0.001]. (B) Quantitative measurements and representative blots showing that SB203580 inhibited not only p38 activation but also the activation of the JNK pathway induced by malonate. For this, rats were killed 6 h after treatment. Statistical analysis yielded the following results: for cytosolic p-p38 [F_(3,30) = 13.29, P < 0.001] and total p38 [F_(3,20) = 16.60, P < 0.001], for nuclear p-p38 [t₍₁₂₎ = 5.319, P < 0.05] and total p38 [t₍₁₂₎ = 3.409, P < 0.05], for p-JNK/JNK (46 kDa) [t₍₁₁₎ = 2.531, P < 0.05] and p-JNK/JNK (54 kDa) [t₍₁₁₎ = 4.591, P < 0.05] and for p-c-jun [t₍₈₎ = 5.292, P < 0.01]. Different from the corresponding sham group: ***P < 0.001. Different from malonate-only animals: ^§P < 0.05; ^§§P < 0.01.