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Protein tyrosine phosphatase deficiency…

Figure 3.- PTP1B-deficient hepatocytes are protected against APAP-induced caspase-3
activation. PTP1B+/+ and PTP1B-/- immortalized hepatocytes were treated with various doses of
APAP for 8 h. A. Analysis of caspase-3 enzymatic activity. B. Analysis of the active caspase-3
fragment in total cell lysates by Western blot. *P<0.05 and ***P<0.005 PTP1B-/- vs. PTP1B+/+ cells
(n=4 independent experiments).

Effect of APAP treatment in the cell cycle of wild-type and PTP1B-/- hepatocytes.
We next investigated the effects of APAP in the distribution of the

hepatocytes along the phases of the cell cycle including the hypodiploid (sub
G0/G1) population. In wild-type hepatocytes, APAP treament induced cell cycle
arrest in S phase with a maximal effect at 0.5 mM dose. Of note, under these
experimental conditions a twofold increase in the percentage of S phase arrested
cells was observed (Figure 5A). This effect was significantly ameliorated in
hepatocytes lacking PTP1B. We also observed that APAP treatment increased the
percentage of hypodiploid cells in wild-type hepatocytes, but again this effect was
significantly reduced in PTP1B-/- hepatocytes (Figure 5B). This result indicates an
apoptotic effect of APAP which was significantly reduced in hepatocytes lacking
PTP1B.

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