Inhibition of Protein-tyrosine Phosphatase PTP1B and LMPTP Promotes Palmitate/Oleate-challenged HepG2 Cell Survival by Reducing Lipoapoptosis, Improving Mitochondrial Dynamics and Mitigating Oxidative and Endoplasmic Reticulum Stress

抑制蛋白酪氨酸磷酸酶 PTP1B 和 LMPTP 可减少脂质细胞凋亡、改善线粒体动力学并减轻氧化和内质网应激,从而促进棕榈酸/油酸刺激的 HepG2 细胞存活

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作者:Lynda Bourebaba, Jacek Łyczko, Michalina Alicka, Nabila Bourebaba, Antoni Szumny, Andrzej M Fal, Krzysztof Marycz

Conclusion

In conclusion, PTP's inhibitory properties may be a promising therapeutic strategy for the treatment of FFA-induced lipotoxicity in the liver and ultimately in the management of the NAFLD condition.

Methods

HepG2 cells were cultured in the presence or absence of two PTP inhibitors, namely MSI-1436 and Compound 23, prior to palmitate/oleate overloading. Apoptosis, ER stress, oxidative stress, and mitochondrial dynamics were then evaluated by either MUSE or RT-qPCR analysis.

Results

The obtained data demonstrate that the inhibition of PTP1B and LMPTP prevents apoptosis induced by palmitate and oleate in the HepG2 cell line. Moreover, mitochondrial dynamics were positively improved following inhibition of the enzyme, with concomitant oxidative stress reduction and ER stress abrogation.

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