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. 2019 Oct 3;10(10):742. doi: 10.1038/s41419-019-1976-4

Fig. 7. PEDF induces AMPK degradation through the ubiquitin–proteasome system.

Fig. 7

a, b Cycloheximide chase assay of AMPK and pAMPK. a HepG2 cells transiently transfected with vector (CON) or PEDF (PEDF) plasmids were treated with cycloheximide (CHX, 10 μg/ml) for indicated time points and then collected for western blotting analysis. AMPK and pAMPK protein signals were quantified, the data were log-transformed, and the protein half-lives were calculated as described in “Materials and Methods” (mean ± SD, ****p < 0.0001, n = 3). b HepG2 cells transfected with PEDF (PEDF) plasmid were treated with DMSO or MG132 (10 μmol/l) in the presence of CHX (10 μg/ml) for indicated time points and then collected for western blotting analysis. AMPK and pAMPK protein signals were quantified and the data were plotted (mean ± SD, ****p < 0.0001, n = 3). c, d HepG2 cells transiently transfected with CON or PEDF plasmids were treated with DMSO or MG132 (10 μmol/L) for 12 h, and then immunoprecipitated with an c AMPK antibody or d pAMPK antibody. The ubiquitination level of AMPK or pAMPK was determined using an anti-ubiquitin antibody. IB, immunoblotting; IP, immunoprecipitation. e Overview of the dual regulation of PEDF on HCC tumor development. On one hand, intracellular PEDF inhibits the activation of AMPK, which activates lipogenesis pathway by increasing FASN expression and suppresses FFA oxidation pathway by decreasing CPT1α expression, leads to elevated FFA levels, and eventually promotes HCC cell proliferation. On the other hand, secreted PEDF performs as a classic anti-angiogenic factor that inhibits tumor angiogenesis in HCC progression. Taken together, PEDF might present dual regulatory effects on HCC development