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10.1371/journal.pone.0086620

http://scihub22266oqcxt.onion/10.1371/journal.pone.0086620
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24497960!3908935!24497960
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suck abstract from ncbi


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pmid24497960      PLoS+One 2014 ; 9 (1): e86620
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  • Cobalt and nickel stabilize stem cell transcription factor OCT4 through modulating its sumoylation and ubiquitination #MMPMID24497960
  • Yao Y; Lu Y; Chen WC; Jiang Y; Cheng T; Ma Y; Lu L; Dai W
  • PLoS One 2014[]; 9 (1): e86620 PMID24497960show ga
  • Stem cell research can lead to the development of treatments for a wide range of ailments including diabetes, heart disease, aging, neurodegenerative diseases, spinal cord injury, and cancer. OCT4 is a master regulator of self-renewal of undifferentiated embryonic stem cells. OCT4 also plays a crucial role in reprogramming of somatic cells into induced pluripotent stem (iPS) cells. Given known vivo reproductive toxicity of cobalt and nickel metals, we examined the effect of these metals on expression of several stem cell factors in embryonic Tera-1 cells, as well as stem cells. Cobalt and nickel induced a concentration-dependent increase of OCT4 and HIF-1alpha, but not NANOG or KLF4. OCT4 induced by cobalt and nickel was due primarily to protein stabilization because MG132 stabilized OCT4 in cells treated with either metals and because neither nickel nor cobalt significantly modulated its steady-state mRNA level. OCT4 stabilization by cobalt and nickel was mediated largely through reactive oxygen species (ROS) as co-treatment with ascorbic acid abolished OCT4 increase. Moreover, nickel and cobalt treatment increased sumoylation and mono-ubiquitination of OCT4 and K123 was crucial for mediating these modifications. Combined, our observations suggest that nickel and cobalt may exert their reproductive toxicity through perturbing OCT4 activity in the stem cell compartment.
  • |Animals[MESH]
  • |Blotting, Western[MESH]
  • |Cell Culture Techniques[MESH]
  • |Cell Line, Tumor[MESH]
  • |Cells, Cultured[MESH]
  • |Cobalt/*pharmacology[MESH]
  • |Dose-Response Relationship, Drug[MESH]
  • |HEK293 Cells[MESH]
  • |Humans[MESH]
  • |Hypoxia-Inducible Factor 1, alpha Subunit/genetics/metabolism[MESH]
  • |Kruppel-Like Factor 4[MESH]
  • |Lysine/genetics/metabolism[MESH]
  • |Mice[MESH]
  • |Mutation[MESH]
  • |Nickel/*pharmacology[MESH]
  • |Octamer Transcription Factor-3/genetics/*metabolism[MESH]
  • |Protein Processing, Post-Translational/drug effects[MESH]
  • |Reverse Transcriptase Polymerase Chain Reaction[MESH]
  • |Stem Cells/*drug effects/metabolism[MESH]
  • |Sumoylation/drug effects[MESH]
  • |Time Factors[MESH]
  • |Transcriptional Activation/drug effects[MESH]


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