Vulnerability of Subcellular Structures to Pathogenesis Induced by Rotenone in SH-SY5Y Cells

Abstract

Numerous pathological changes of subcellular structures are characteristic hallmarks of neurodegeneration. The main research has focused to mitochondria, endoplasmic reticulum, Golgi apparatus, lysosomal networks as well as microtubular system of the cell. The sequence of specific organelle damage during pathogenesis has not been answered yet. Exposition to rotenone is used for simulation of neurodegenerative changes in SH-SY5Y cells, which are widely used for in vitro modelling of Parkinson´s disease pathogenesis. Intracellular effects were investigated in time points from 0 to 24 h by confocal microscopy and biochemical analyses. Analysis of fluorescent images identified the sensitivity of organelles towards rotenone in this order: microtubular cytoskeleton, mitochondrial network, endoplasmic reticulum, Golgi apparatus and lysosomal network. All observed morphological changes of intracellular compartments were identified before αS protein accumulation. Therefore, their potential as an early diagnostic marker is of interest. Understanding of subcellular sensitivity in initial stages of neurodegeneration is crucial for designing new approaches and a management of neurodegenerative disorders.

Liposomes loaded with polyphenol-rich grape pomace extracts protect from neurodegeneration in a rotenone-based in vitro model of Parkinson's disease

“…Rotenone is an inhibitor of the mitochondrial electron transport chain complex I commonly used to induce PD-like features both in vivo and in vitro. [39][40][41] In particular, we assessed the ability of ext-LSs to reduce ROS, to improve cell viability, and to hinder α-syn aggregation in the in vitro PD model.…”

Correlation between α-synuclein and fatty acid composition in jejunum of rotenone-treated mice is dependent on acyl chain length

“…Despite that we did not measure αS in present in vitro experiments, our previous study identified 10 μM rotenone treatment for 24 h as an effective in stimulation of αS overexpression in SH-SY5Y cells. In addition, the fragmentation of microtubules, mainly composed by BIIIT, was confirmed as a rapid action associated with rotenone presence in the cell culture (Pokusa et al 2021). In the case of mouse model, an increase in the expression of αS was identified in jejunum of several individuals after 14 weeks of rotenone treatment while in the case of control animals αS was under the detection limit of chosen ELISA test in all individuals (Fig.…”

“…The inhibition of mitochondrial electron chain complex I, which can be achieved using rotenone, represents one of the platforms for αS overexpression in experimental in vivo and in vitro PD models (Giráldez-Pérez et al 2014;Pokusa et al 2021). In comparison to genetic or other toxic models of PD, the rotenone model is widely used especially due to the capability to recapitulate wide spectrum of pathological signs of PD (Shimohama et al 2003).…”