PMID- 29762523 OWN - NLM STAT- MEDLINE DCOM- 20180921 LR - 20240318 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 19 IP - 5 DP - 2018 May 15 TI - Silver Nanoparticles: Two-Faced Neuronal Differentiation-Inducing Material in Neuroblastoma (SH-SY5Y) Cells. LID - 10.3390/ijms19051470 [doi] LID - 1470 AB - We have previously demonstrated the potential of biologically synthesized silver nanoparticles (AgNP) in the induction of neuronal differentiation of human neuroblastoma, SH-SY5Y cells; we aimed herein to unveil its molecular mechanism in comparison to the well-known neuronal differentiation-inducing agent, all-trans-retinoic acid (RA). AgNP-treated SH-SY5Y cells showed significantly higher reactive oxygen species (ROS) generation, stronger mitochondrial membrane depolarization, lower dual-specificity phosphatase expression, higher extracellular-signal-regulated kinase (ERK) phosphorylation, lower AKT phosphorylation, and lower expression of the genes encoding the antioxidant enzymes than RA-treated cells. Notably, pretreatment with N-acetyl-l-cysteine significantly abolished AgNP-induced neuronal differentiation, but not in that induced by RA. ERK inhibition, but not AKT inhibition, suppresses neurite growth that is induced by AgNP. Taken together, our results uncover the pivotal contribution of ROS in the AgNP-induced neuronal differentiation mechanism, which is different from that of RA. However, the negative consequence of AgNP-induced neurite growth may be high ROS generation and the downregulation of the expression of the genes encoding the antioxidant enzymes, which prompts the future consideration and an in-depth study of the application of AgNP-differentiated cells in neurodegenerative disease therapy. FAU - Abdal Dayem, Ahmed AU - Abdal Dayem A AD - Department of Stem Cell and Regenerative Biotechnology, Incurable Disease Animal Model & Stem Cell Institute (IDASI), Konkuk University, Seoul 05029, Korea. ahmed_morsy86@yahoo.com. FAU - Lee, Soo Bin AU - Lee SB AD - Department of Stem Cell and Regenerative Biotechnology, Incurable Disease Animal Model & Stem Cell Institute (IDASI), Konkuk University, Seoul 05029, Korea. soobineey@naver.com. FAU - Choi, Hye Yeon AU - Choi HY AD - Department of Stem Cell and Regenerative Biotechnology, Incurable Disease Animal Model & Stem Cell Institute (IDASI), Konkuk University, Seoul 05029, Korea. hyeon.choi24@gmail.com. FAU - Cho, Ssang-Goo AU - Cho SG AUID- ORCID: 0000-0002-0968-7932 AD - Department of Stem Cell and Regenerative Biotechnology, Incurable Disease Animal Model & Stem Cell Institute (IDASI), Konkuk University, Seoul 05029, Korea. ssangoo@konkuk.ac.kr. LA - eng PT - Journal Article DEP - 20180515 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Reactive Oxygen Species) RN - 3M4G523W1G (Silver) RN - 5688UTC01R (Tretinoin) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3) RN - WYQ7N0BPYC (Acetylcysteine) SB - IM MH - Acetylcysteine/pharmacology MH - Cell Line, Tumor MH - Humans MH - Membrane Potential, Mitochondrial MH - Metal Nanoparticles/*chemistry MH - Mitogen-Activated Protein Kinase 3/metabolism MH - Neuroblastoma/*metabolism MH - *Neurogenesis MH - Neurons/cytology/*drug effects/metabolism MH - Reactive Oxygen Species/metabolism MH - Silver/chemistry MH - Tretinoin/pharmacology PMC - PMC5983825 OTO - NOTNLM OT - differentiation OT - kinase OT - mitochondria OT - neuroblastoma OT - phosphatase OT - reactive oxygen species OT - silver nanoparticles COIS- The authors declare no conflicts of interest. EDAT- 2018/05/16 06:00 MHDA- 2018/09/22 06:00 PMCR- 2018/05/01 CRDT- 2018/05/16 06:00 PHST- 2018/04/16 00:00 [received] PHST- 2018/05/08 00:00 [revised] PHST- 2018/05/11 00:00 [accepted] PHST- 2018/05/16 06:00 [entrez] PHST- 2018/05/16 06:00 [pubmed] PHST- 2018/09/22 06:00 [medline] PHST- 2018/05/01 00:00 [pmc-release] AID - ijms19051470 [pii] AID - ijms-19-01470 [pii] AID - 10.3390/ijms19051470 [doi] PST - epublish SO - Int J Mol Sci. 2018 May 15;19(5):1470. doi: 10.3390/ijms19051470.