Biologically synthesized silver nanoparticles induce neuronal differentiation of SH‐SY5Y cells via modulation of reactive oxygen species, phosphatases, and kinase signaling pathways

Abstract

Nano-scale materials are noted for unique properties, distinct from those of their bulk material equivalents. In this study, we prepared spherical silver nanoparticles (AgNPs) with an average size of about 30 nm and tested their potency to induce neuronal differentiation of SH-SY5Y cells. Human neuroblastoma SH-SY5Y cells are considered an ideal in vitro model for studying neurogenesis, as they can be maintained in an undifferentiated state or be induced to differentiate into neuron-like phenotypes in vitro by several differentiation-inducing agents. Treatment of SH-SY5Y cells by biologically synthesized AgNPs led to cell morphological changes and significant increase in neurite length and enhanced the expression of neuronal differentiation markers such as Map-2, β-tubulin III, synaptophysin, neurogenin-1, Gap-43, and Drd-2. Furthermore, we observed an increase in generation of intracellular reactive oxygen species (ROS), activation of several kinases such as ERK and AKT, and downregulation of expression of dual-specificity phosphatases (DUSPs) in AgNPs-exposed SH-SY5Y cells. Our results suggest that AgNPs modulate the intracellular signaling pathways, leading to neuronal differentiation, and could be applied as promising nanomaterials for stem cell research and therapy.

Dual functions of silver nanoparticles in F9 teratocarcinoma stem cells, a suitable model for evaluating cytotoxicity- and differentiation-mediated cancer therapy

“…25 AgNPs have been shown to induce neuronal differentiation of SH-SY5Y cells via modulation of ROS, phosphatases, and kinase signaling pathways. 26 In another study, substrates coated with AgNPs, which serve as favorable anchoring sites, showed significantly enhanced neurite outgrowth. 27 Androgen deprivation and chemical compounds were found to induce differentiation of neuroendocrine cells in prostate cancer.…”

Quercetin-mediated synthesis of graphene oxide–silver nanoparticle nanocomposites: a suitable alternative nanotherapy for neuroblastoma

“…The cells can also be maintained in an undifferentiated state. [7][8][9] SH-SY5Y cells exhibit properties of stem cells and differentiate upon treatment with a variety of agents, including retinoic acid and silver nanoparticles (AgNPs). 7,10,11 Consequently, the SH-SY5Y cell line has been widely used in analyses of neuronal differentiation, metabolism, neurodegenerative and neuro-adaptive processes, neurotoxicity, and neuroprotection.…”

“…[7][8][9] SH-SY5Y cells exhibit properties of stem cells and differentiate upon treatment with a variety of agents, including retinoic acid and silver nanoparticles (AgNPs). 7,10,11 Consequently, the SH-SY5Y cell line has been widely used in analyses of neuronal differentiation, metabolism, neurodegenerative and neuro-adaptive processes, neurotoxicity, and neuroprotection. 6,10,12 Therefore, the selection of classical cellular models is critical to dissect the functional aspects and molecular mechanisms of action of new molecules, potential toxins, or cytotoxic agents.…”

“…7,8 Cells were grown to confluence at 37°C in a 5% CO 2 atmosphere. All experiments were performed in 96-well plates and 100 mm cell culture dishes.…”

Differential nanoreprotoxicity of silver nanoparticles in male somatic cells and spermatogonial stem cells

“…20,63 Intracellular ROS have been reported to be a crucial indicator of various toxic effects exerted by nanoparticles. 67,68 Previous studies have shown that AgNPs-induced ROS generation reduces survival of different types of cells.…”