title: H2O2 treatment or serum deprivation induces autophagy and apoptosis in naked mole-rat skin fibroblasts by inhibiting the PI3K/Akt signaling pathway.
abstract: 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.
authors.affiliation: Laboratory Animal Centre, Second Military Medical University, Shanghai, China.
authors.forename: Shanmin
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Training, Second Military Medical University, Shanghai, China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Informatization Office, Second Military Medical University, Shanghai, China.
authors.forename: Shiyong
authors.initials: S
authors.lastname: Wang
authors.affiliation: Laboratory Animal Centre, Second Military Medical University, Shanghai, China.
authors.forename: Chenlin
authors.initials: C
authors.lastname: Yu
authors.affiliation: Laboratory Animal Centre, Second Military Medical University, Shanghai, China.
authors.forename: Bang
authors.initials: B
authors.lastname: Xiao
authors.affiliation: Laboratory Animal Centre, Second Military Medical University, Shanghai, China.
authors.forename: Lifang
authors.initials: L
authors.lastname: Lin
authors.affiliation: Laboratory Animal Centre, Second Military Medical University, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Cong
authors.affiliation: Laboratory Animal Centre, Second Military Medical University, Shanghai, China.
authors.forename: Jishuai
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Laboratory Animal Centre, Second Military Medical University, Shanghai, China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Yang
authors.affiliation: Laboratory Animal Centre, Second Military Medical University, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Sun
authors.affiliation: Laboratory Animal Centre, Second Military Medical University, Shanghai, China.
authors.forename: Shufang
authors.initials: S
authors.lastname: Cui
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D002478:Cells, Cultured; D002738:Chloroquine / Q000494:pharmacology*; D002867:Chromones / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation; D006861:Hydrogen Peroxide / Q000378:metabolism; D008136:Longevity; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D019577:Mole Rats / Q000502:physiology*; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D012867:Skin / Q000473:pathology*
chemical_list: D002867:Chromones; D008869:Microtubule-Associated Proteins; D009025:Morpholines; D019253:Proto-Oncogene Proteins c-bcl-2; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D002738:Chloroquine; D006861:Hydrogen Peroxide; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa
keywords: apoptosis; autophagy; naked mole-rats