Mitochondrial Peptide Humanin Protects Silver Nanoparticles-Induced Neurotoxicity in Human Neuroblastoma Cancer Cells (SH-SY5Y)

Abstract

The extensive usage of silver nanoparticles (AgNPs) as medical products such as antimicrobial and anticancer agents has raised concerns about their harmful effects on human beings. AgNPs can potentially induce oxidative stress and apoptosis in cells. However, humanin (HN) is a small secreted peptide that has cytoprotective and neuroprotective cellular effects. The aim of this study was to assess the harmful effects of AgNPs on human neuroblastoma SH-SY5Y cells and also to investigate the protective effect of HN from AgNPs-induced cell death, mitochondrial dysfunctions, DNA damage, and apoptosis. AgNPs were prepared with an average size of 18 nm diameter to study their interaction with SH-SY5Y cells. AgNPs caused a dose-dependent decrease of cell viability and proliferation, induced loss of plasma-membrane integrity, oxidative stress, loss of mitochondrial membrane potential (MMP), and loss of ATP content, amongst other effects. Pretreatment or co-treatment of HN with AgNPs protected cells from several of these AgNPs induced adverse effects. Thus, this study demonstrated for the first time that HN protected neuroblastoma cells against AgNPs-induced neurotoxicity. The mechanisms of the HN-mediated protective effect on neuroblastoma cells may provide further insights for the development of novel therapeutic agents against neurodegenerative diseases.

Long non-coding RNA LINC00649 regulates YES-associated protein 1 (YAP1)/Hippo pathway to accelerate gastric cancer (GC) progression via sequestering miR-16-5p

“…To our knowledge, Hippo pathway sustained normal cellular functions to suppress cancer aggressiveness and development [29,30]. However, the normal cells acquired malignant phenotypes and turned into cancer cells when the Hippo pathway dysregulated [31,32], and recent publications reported that dysregulation of the Hippo pathway accelerated GC progression [33][34][35]. As previously described, the downstream Yes-associated protein 1 (YAP1) was proved as an oncogene to facilitate pathogenesis of multiple cancers [36], such as pancreatic cancer [37], lung cancer [38], and GC [39].…”

Mechanisms of protection of retinal pigment epithelial cells from oxidant injury by humanin and other mitochondrial-derived peptides: Implications for age-related macular degeneration

“… Neuroblastoma cell line (SH-SY5Y). Human HN-silver Nanoparticles Neuroprotection [ 102 ] Alzheimer's disease Cortical neurons Rats HN Attenuation of NMDA- excitotoxicity, improvement of mitochondrial function [ 103 , 104 ] Alzheimer's disease Brain Mice HNG Improved cognitive function [ 105 , 106 ] Alzheimer's disease Brain Rats HNG Reversal of impairment of spatial memory [ 107 ] Alzheimer's disease Brain Mice HNG Decreased Aβ level and ameliorated cognitive impairment. [ 108 ] Alzheimer's disease Brain Rats HN Amelioration of memory deficits induced by Aβ (1-42).…”

“…Cellular mitochondrial oxidative capacity is correlated with the number and size of mitochondria [ 146 ]. The dysregulation of mitochondrial biogenesis and dynamics due to oxidative stress leads to a decrease in mtDNA copy number, mitochondrial number, mitochondrial mass and oxidative capacity [ 35 , 102 , 147 ]. Thus, enhanced mitochondrial biogenesis could be one of the mechanisms by which cells regulate mitochondrial bioenergetics.…”

“…Treatment with HN inhibited mitochondrial ROS by elevating mGSH [ 36 ]. In addition, ER homeostasis can be disrupted by intracellular calcium (Ca 2+) level, redox status, and energy stores, culminating in ER stress [ 41 , 60 , 102 , 157 ]. Given the known role of calcium in ER stress, HN-mediated cytoprotection could partially result from HN's ability to decrease intracellular calcium release under stress [ 158 ].…”

“…It is well established that ER stress is regulated by three transmembrane sense proteins: inositol-requiring enzyme 1 (IRE1), PKR-like ER kinase (PERK), and activating transcription factor 6 (ATF6) [ 157 , 159 ]. HN markedly decreased the expression of all the transmembrane sense proteins (IRE, PERK and ATF-6) and improved cell survival in SH-SY5Y cells [ 102 ]. However, direct visualization of HN location in the ER of cells, or HN potential translocation from the mitochondria into ER, which would provide a better understanding of the role of HN mito-ER cross talk, is lacking.…”