Small molecule compounds alleviate anisomycin-induced oxidative stress injury in SH-SY5Y cells via downregulation of p66shc and Aβ1–42 expression

Abstract

Abstract. Oxidative stress and ageing are important factors contributing to the pathogenesis of Alzheimer's disease (AD), which is associated with neuronal damage and β-amyloid (Aβ) deposition. The p66shc adaptor protein is important for the regulation of oxidative stress and ageing. In the present study, SH-SY5Y human neuroblastoma cells were treated with anisomycin in order to establish a cell model of oxidative stress-induced neuronal damage. The results from quantitative polymerase chain reaction, enzyme-linked immunosorbent assay and western blotting demonstrated that anisomycin was able to stimulate the secretion of Aβ1-42 from SH-SY5Y cells and upregulate the expression levels of p66shc, which was associated with concomitant damage to SH-SY5Y cells. In addition, the protective effects of various small molecule compounds with antioxidant properties against neuronal damage were evaluated. Notably, treatment of SH-SY5Y cells with gallic acid was associated with significant downregulation of p66shc protein expression levels, reduced anisomycin-induced secretion of Aβ1-42, and increased superoxide dismutase activity and acetylcholine secretion levels. The results of the present study suggested that anisomycin is able to promote oxidative neuronal damage by inducing the secretion of Aβ1-42 from neurons and increasing the neuronal expression of p66shc, and this damage may be attenuated by treatment with gallic acid. Therefore, gallic acid and similar small molecule compounds may be considered for the alleviation of neuronal oxidative stress injury in patients with AD.

Ethyl Acetate Extract Components of Bushen-Yizhi Formula Provides Neuroprotection against Scopolamine-induced Cognitive Impairment

“…Hence, we study different types of BSYZ-F extracts to investigate the effective components of BSYZ-F. We verify that the ethyl acetate extract components (BSYZ-E) is the most effective extract of BSYZ-F. Gallic acid, 4-Hydroxybenzoic acid, 2,3,5,4′-tetrahydroxylstilbene-2-O-β-D-glucoside, Xanthotoxol, methoxsalen, isopimpinellin, bergapten, imperatorin, prangenidin, osthole and emodin are identified as the most abundant monomer compounds in BSYZ-E. These small molecules have been shown to have anti-cholinesterase, anti-apoptotic, anti-oxidative effects and be related with synaptic growth 21 – 27 . All of the compounds from BSYZ-E are the pharmacodynamic substance foundation.…”

Anisomycin has a potential toxicity of promoting cuproptosis in human ovarian cancer stem cells by attenuating YY1/lipoic acid pathway activation

“…Anisomycin (3,4-Pyrrolidinediol, 2-[(4-methoxyphenyl) methyl] -, 3-acetate, (2R, 3S, 4S) is an antibiotic purified from Streptomyces griseus [20] that inhibits peptide bond formation and inhibits protein synthesis by binding to 60S ribosomal subunits [20][21][22]. Anisomycin is also a c-Jun N-terminal kinase (JNK) activator that enhances the phosphorylation of JNK [23,24].…”

Dual role of an essential HtrA2/Omi protease in the human malaria parasite: maintenance of mitochondrial homeostasis and induction of apoptosis like cell death under cellular stress

“…HtrA2 has been shown to perform a dual function in the eukaryotic cell, in addition to acting as a mitochondrial chaperone, as described above, it can also act as a protease to regulate cellular proteins. In neural cells, loss of proteolytic function of HtrA2 results in accumulation of its direct substrate, p66Shc, which cause ROS generation and induction of apoptosis [39][40][41]. Although, direct substrate of PfHtrA2 are not known in Plasmodium, but we show that PfHtrA2-iKD caused increase in mitochondrial ROS levels and parasite death.…”