Cell quality control mechanisms maintain stemness and differentiation potential of P19 embryonic carcinoma cells.

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 BStem cellCellular differentiationATF6SOX2Mechanistic target of rapamycinCell biologyPI3K/AKT/mTOR pathwayHomeobox protein NANOGBiology

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.

参考文章(86)
Lorenzo Galluzzi, Federico Pietrocola, Beth Levine, Guido Kroemer, Metabolic Control of Autophagy Cell. ,vol. 159, pp. 1263- 1276 ,(2014) , 10.1016/J.CELL.2014.11.006
R Palorini, F P Cammarata, C Balestrieri, A Monestiroli, M Vasso, C Gelfi, L Alberghina, F Chiaradonna, Glucose starvation induces cell death in K-ras-transformed cells by interfering with the hexosamine biosynthesis pathway and activating the unfolded protein response. Cell Death and Disease. ,vol. 4, pp. 1- 14 ,(2013) , 10.1038/CDDIS.2013.257
Giuseppe Petrosillo, Valentina De Benedictis, Francesca M. Ruggiero, Giuseppe Paradies, Decline in cytochrome c oxidase activity in rat-brain mitochondria with aging. Role of peroxidized cardiolipin and beneficial effect of melatonin. Journal of Bioenergetics and Biomembranes. ,vol. 45, pp. 431- 440 ,(2013) , 10.1007/S10863-013-9505-0
R. Taneja, B. Roy, J. L. Plassat, C. F. Zusi, J. Ostrowski, P. R. Reczek, P. Chambon, Cell-type and promoter-context dependent retinoic acid receptor (RAR) redundancies for RAR beta 2 and Hoxa-1 activation in F9 and P19 cells can be artefactually generated by gene knockouts Proceedings of the National Academy of Sciences of the United States of America. ,vol. 93, pp. 6197- 6202 ,(1996) , 10.1073/PNAS.93.12.6197
Shuling Zhang, Julie A. Readinger, Wendy DuBois, Mirkka Janka-Junttila, Richard Robinson, Margaret Pruitt, Val Bliskovsky, Julie Z. Wu, Kaori Sakakibara, Jyoti Patel, Carole A. Parent, Lino Tessarollo, Pamela L. Schwartzberg, Beverly A. Mock, Constitutive reductions in mTOR alter cell size, immune cell development, and antibody production Blood. ,vol. 117, pp. 1228- 1238 ,(2011) , 10.1182/BLOOD-2010-05-287821
Peter van Galen, Antonija Kreso, Nathan Mbong, David G Kent, Timothy Fitzmaurice, Joseph E Chambers, Stephanie Xie, Elisa Laurenti, Karin Hermans, Kolja Eppert, Stefan J Marciniak, Jane C Goodall, Anthony R Green, Bradly G Wouters, Erno Wienholds, John E Dick, None, The unfolded protein response governs integrity of the haematopoietic stem-cell pool during stress Nature. ,vol. 510, pp. 268- 272 ,(2014) , 10.1038/NATURE13228
Giuseppe Petrosillo, Francesca M. Ruggiero, Giuseppe Paradies, Role of reactive oxygen species and cardiolipin in the release of cytochrome c from mitochondria The FASEB Journal. ,vol. 17, pp. 2202- 2208 ,(2003) , 10.1096/FJ.03-0012COM
J Zhang, P A Ney, ROLE OF BNIP3 AND NIX IN CELL DEATH, AUTOPHAGY, AND MITOPHAGY Cell Death & Differentiation. ,vol. 16, pp. 939- 946 ,(2009) , 10.1038/CDD.2009.16
Amar M. Singh, David Reynolds, Timothy Cliff, Satoshi Ohtsuka, Alexa L. Mattheyses, Yuhua Sun, Laura Menendez, Michael Kulik, Stephen Dalton, Signaling Network Crosstalk in Human Pluripotent Cells: A Smad2/3-Regulated Switch that Controls the Balance between Self-Renewal and Differentiation Cell Stem Cell. ,vol. 10, pp. 312- 326 ,(2012) , 10.1016/J.STEM.2012.01.014
Derek P. Narendra, Richard J. Youle, Targeting Mitochondrial Dysfunction: Role for PINK1 and Parkin in Mitochondrial Quality Control Antioxidants & Redox Signaling. ,vol. 14, pp. 1929- 1938 ,(2011) , 10.1089/ARS.2010.3799