Table 2

Relative expression of PPARα protein in mouse and human liver lysates

Mouse strainAgeSexComplex I preimmune serum2-aComplex I anti-PPARα2-aShifted by anti-PPARα2-b
%
CD-111wF4.93  ± 0.95  (3)2-c 0.92  ± 0.40  (3)2-c 81.2  ± 6.7  (3)2-c
BALB/cByJ11wF4.47  ± 3.34  (3)2-c 0.88  ± 0.68  (3)2-c 80.7  ± 0.7  (3)2-c
Human samplesLiver function tests2-fAgeSexComplex I preimmune serum2-aComplex I anti-PPARα2-aShifted by anti-PPARα2-b
ID2-dClin. Hist.2-e
AALCN.A.57F0.44 0.28 36.4 
BRx, FLN.A.60F0.46 0.31 32.6 
DRx, FLN.A.42M0.93 0.68 26.9 
KALCN.A., DM66M1 0.41 58.8 
QNRM, DM24F0.84 0.31 63.1 
RELV36M1.27 0.74 41.7 
UNRM22M0.87 0.64 26.4 
 Mean ± standard deviation0.83  ± 0.27  (7)2-c 0.48  ± 0.18  (7)2-c 40.8  ± 13.7  (7)2-c
CRx, FLN.A.57F0.41 0.39 N.S.
EN.A.3M0.5  0.47 N.S.2-g
FN.A.60F0.13 0.14 N.S.
GRx, FLN.A.35M0.26 0.22 N.S.
HNRM, DM8F0.28 0.28 N.S.
MRx, FL, DBN.A.52F0.63 0.61 N.S.
NALC, Rx, FLN.A.40F0.74 0.67 N.S.
ONRM14M0.54 0.54 N.S.
PELV7M0.96 0.79 N.S.
SELV6M0.41 0.4  N.S.
 Mean ± standard deviation0.49  ± 0.23  (10)2-c 0.45  ± 0.20  (10)2-c
INRM10MN.D.2-h
JNRM, DM6MN.D.
LN.A.?FN.D.
  • 2-a The amounts of complex I obtained for each liver lysate with the labeled CYP4A6 Z element in the presence of preimmune serum or anti-PPARα serum was measured using a PhosphorImager and electrophoretic mobility shift assays. The results were normalized on the basis of total protein in the sample and are expressed relative to the value obtained for human liver lysate K in the presence of preimmune serum.

  • 2-b The percentage is the difference obtained by subtracting the amount of complex I determined in the presence of anti-PPARα from the amount found in the presence of preimmune serum and is expressed as a percentage of the amount obtained in the presence of the preimmune serum.

  • 2-c Values are given as mean ± standard deviation with number of samples in parentheses.

  • 2-d Sample identifiers correspond to samples depicted in Fig.4-6 and Table 1.

  • 2-e Clinical history: ALC, alcohol; FL, moderate fatty liver; DB, diabetes (type II); Rx, medications (human B, phenytoin, labetolol, furosamide, verapamil, dexamethasone, ranitidine, vasopressin; human C, loop diuretic predisone, vasotec; human D, phenytoin, cimetidine, insulin, cephalosporin (Ancef); human G, cocaine; human M, gemfibrozil, estrogen, tolbutamide, tricyclic antidepressant, aspirin, cardiofem nitrate; human N, allopurinal, cephalosporin, methylprednisone).

  • 2-f NRM indicates that the following liver function tests were performed: total bilirubin, glutamate oxaloacetate transferase, glutamate pyruvate transferase, lactate dehydrogenase, and prothrombin time. The samples displayed normal levels. In some cases (ELV), levels above normal ranges were found in some of the tests. The elevated enzyme levels are probably due to the injury rather than to poor liver function. DM indicates that microsomes were prepared from the tissue sample and were used successfully for kinetic assays to determine P450 2C8, 2C9, 2C18, 2C19, and 3A catalytic activity (Jung et al., 1997). N.A., not available.

  • 2-g N.S., the percent difference is less than the interassay variation for the signal intensity.

  • 2-h N.D., the signal intensity is less than twice background levels.