作者: Silvia Magalhães-Novais , Juan C. Bermejo-Millo , Rute Loureiro , Katia A. Mesquita , M. Rosário Domingues
DOI: 10.1080/15548627.2019.1607694
关键词: Protein kinase B 、 Stem cell 、 Cellular differentiation 、 ATF6 、 SOX2 、 Mechanistic target of rapamycin 、 Cell biology 、 PI3K/AKT/mTOR pathway 、 Homeobox protein NANOG 、 Biology
摘要: Given the relatively long life of stem cells (SCs), efficient mechanisms quality control to balance cell survival and resistance external internal stress are required. Our objective was test relevance for SCs maintenance, differentiation death. We compared in P19 (P19SCs) before after (P19dCs). Differentiation P19SCs resulted alterations parameters involved protein homeostasis, including redox system, cardiolipin lipid profiles, unfolded response, ubiquitin-proteasome lysosomal systems, signaling pathways controlling growth. In addition, pluripotency correlated with stronger antioxidant protection, modulation apoptosis, activation macroautophagy, which all contributed preserve by increasing threshold death activation. Furthermore, our findings identify critical roles PI3K-AKT-MTOR pathway, as well autophagic flux apoptosis regulation maintenance potential.Abbreviations: 3-MA: 3-methyladenine; AKT/protein kinase B: thymoma viral proto-oncogene; AKT1: proto-oncogene 1; ATG: AuTophaGy-related; ATF6: activating transcription factor 6; BAX: BCL2-associated X protein; BBC3/PUMA: BCL2 binding component 3; BCL2: B leukemia/lymphoma 2; BNIP3L: BCL2/adenovirus E1B interacting 3-like; CASP3: caspase CASP8: 8; CASP9: 9; CL: cardiolipin; CTSB: cathepsin B; CTSD: D; DDIT3/CHOP: DNA-damage inducible transcript DNM1L/DRP1: dynamin 1-like; DRAM1: regulated autophagy modulator EIF2AK3/PERK: eukaryotic translation initiation 2 alpha EIF2S1/eIF2α: 2, subunit alpha; ERN1/IRE1α: endoplasmic reticulum nucleus ESCs: embryonic cells; KRT8/TROMA-1: cytokeratin LAMP2A: lysosomal-associated membrane 2A; MAP1LC3/LC3: microtubule-associated 1 light chain MTOR: mechanistic target rapamycin kinase; NANOG: Nanog homeobox; NAO: 10-N-nonyl acridine orange; NFE2L2/NRF2: nuclear factor, erythroid derived like OPA1: OPA1, mitochondrial GTPase; P19dCs: differentiated P19SCs: POU5F1/OCT4: POU domain, class 5, PtdIns3K: phosphatidylinositol 3-kinase; RA: retinoic acid; ROS: reactive oxygen species; RPS6KB1/p70S6K: ribosomal S6 kinase, polypeptide SCs: SOD: superoxide dismutase; SHC1-1/p66SHC: src homology domain-containing transforming C1, 66 kDa isoform; SOX2: SRY (sex determining region Y)-box SQSTM1/p62: sequestosome SPTAN1/αII-spectrin: spectrin alpha, non-erythrocytic TOMM20: translocase outer 20; TRP53/p53: transformation related 53; TUBB3/betaIII-tubulin: tubulin, beta 3 III; UPR: response; UPS: system.