H2O2 treatment or serum deprivation induces autophagy and apoptosis in naked mole-rat skin fibroblasts by inhibiting the PI3K/Akt signaling pathway
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Shanmin Zhao1,*, Li Li2,*, Shiyong Wang3,*, Chenlin Yu1, Bang Xiao1, Lifang Lin1, Wei Cong1, Jishuai Cheng1, Wenjing Yang1, Wei Sun1, Shufang Cui1
1Laboratory Animal Centre, Second Military Medical University, Shanghai, China
2Department of Training, Second Military Medical University, Shanghai, China
3Informatization Office, Second Military Medical University, Shanghai, China
*These authors contributed equally to this work
Shufang Cui, email: [email protected]
Keywords: naked mole-rats, autophagy, apoptosis
Received: August 05, 2016 Accepted: October 28, 2016 Published: November 12, 2016
Naked mole-rats (NMR; Heterocephalus glaber) display extreme longevity and resistance to cancer. Here, we examined whether autophagy contributes to the longevity of NMRs by assessing the effects of the PI3K/Akt pathway inhibitor LY294002 and the autophagy inhibitor chloroquine (CQ) on autophagy and apoptosis in NMR skin fibroblasts. Serum starvation, H2O2 treatment, and LY294002 treatment all increased the LC3-II/LC3-I ratio and numbers of double-membraned autophagosomes and autophagic vacuoles, and decreased levels of p70S6K, p-AktSer473, and p-AktThr308. By contrast, CQ treatment decreased p70S6K, AktSer473, and AktThr308 levels. The Bax/Bcl-2 ratio increased after 12 h of exposure to LY294002 or CQ. These data show that inhibiting the Akt pathway promotes autophagy and apoptosis in NMR skin fibroblasts. Furthermore, LY294002 or CQ treatment decreased caspase-3, p53, and HIF1-α levels, suggesting that serum starvation or H2O2 treatment increase autophagy and apoptosis in NMR skin fibroblasts by inhibiting the PI3K/Akt pathway. CQ-induced inhibition of late autophagy stages also prevented Akt activation and induced apoptosis. Finally, the HIF-1α and p53 pathways were involved in serum starvation- or H2O2-induced autophagy in NMR skin fibroblasts.
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