Rotenone, a neurotoxic pesticide, induces loss of dopaminergic neurons related to Parkinson's disease. Previous studies have shown that rotenone induces neuronal apoptosis partly by triggering hydrogen peroxide (H2O2)-dependent suppression of mTOR pathway. However, the underlying mechanism is not fully understood. Here, we show that rotenone elevates intracellular free calcium ion ([Ca2+]i) lev...

Background on the Chemistry of Rotenone. Rotenone is a natural product isolated from certain subtropical and tropical members of the pea family found in South America and Southeast Asia. The use of rotenone by man may be ancient, as early explorers noted Peruvian natives using crude extracts of the Cubé plant to stun fish for eating. In the early 1900’s, botanists exploring Peruvian jungles sea...

Increasing evidences show that the etiology of Parkinson's disease (PD) is multifactorial. Studying the combined effect of several factors is becoming a hot topic in PD research. On one hand, iron is one of the essential trace metals for human body; on the other hand, iron may be involved in the etiopathogenesis of PD. In our present study, the rats with increased neonatal iron (120 μg/g bodywe...

The mitochondrial toxin rotenone exerts cytotoxicity via overproduction of reactive oxygen species (ROS) and depolarization of the mitochondrial membrane. We investigated the effects of rotenone (12.5, 25, 50, 100 nmol/L) on mitochondrial biogenesis and the potential roles of ROS production in SH-SY5Y cells. Mitochondrial biogenesis was assessed by counting the number of mitochondria, determini...

Autophagy is a self-digestion process important for cell survival during starvation. It has also been described as a form of programmed cell death. Mitochondria are important regulators of autophagy-induced cell death and damaged mitochondria are often degraded by autophagosomes. Inhibition of the mitochondrial electron transport chain (mETC) induces cell death through generating reactive oxyge...

Rotenone inhibits spontaneously and chemically induced hepatic tumorigenesis in rodents through the induction of apoptosis. However, the mechanism for the induction of apoptosis by rotenone has not been defined. Mitochondrial dysfunction, in particular the induction of the mitochondrial membrane permeability transition (MPT), has been implicated in the cascade of events involved in the inductio...

Previous studies showed that augmentation of the autophagy-lysosome process may be beneficial for many neurodegenerative diseases including Parkinson's disease (PD), in which abnormal accumulation aggregated proteins and mitochondrial dysfunctions are considered as crucial pathogenesis. Recently, several have advocated neuroprotective effects intralipid models numerous diseases. In this study, ...

The pesticide rotenone, a neurotoxin that inhibits the mitochondrial complex I, and destabilizes microtubules (MT) has been linked to Parkinson disease (PD) etiology and is often used to model this neurodegenerative disease (ND). Many of the mechanisms of action of rotenone are posited mechanisms of neurodegeneration; however, they are not fully understood. Therefore, the study of rotenone-affe...

Parkinson disease (PD) is a complex neurodegenerative disorder characterized by a progressive loss of dopaminergic neurons. Mitochondrial dysfunction, oxidative stress or protein misfolding and aggregation may underlie this process. Autophagy is an intracellular catabolic mechanism responsible for protein degradation and recycling of damaged proteins and cytoplasmic organelles. Autophagic dysfu...

Rotenone is a naturally derived pesticide that has recently been shown to evoke the behavioral and pathological symptoms of Parkinson's disease in animal models. Though rotenone is known to be an inhibitor of the mitochondrial complex I electron transport chain, little is known about downstream pathways leading to its toxicity. We used human dopaminergic SH-SY5Y cells to study mechanisms of rot...