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Paraquat induces oxidative stress and neuronal cell death; neuroprotection by water-soluble Coenzyme Q10.
Toxicol Appl Pharmacol. 2004 Nov 15; 201(1):21-31.TA

Abstract

Neuronal cell death induced by oxidative stress is correlated with numerous neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and stroke. The causes of sporadic forms of age-related neurodegenerative diseases are still unknown. Recently, a correlation between paraquat exposure and neurodegenerative diseases has been observed. Paraquat, a nonselective herbicide, was once widely used in North America and is still routinely used in Taiwan. We have used differentiated Human Neuroblastoma (SHSY-5Y) cells as an in vitro model to study the mechanism of cell death induced by paraquat. We observed that paraquat-induced oxidative stress in differentiated SHSY-5Y cells as indicated by an increase in the production of cellular reactive oxygen species (ROS). Furthermore, apoptosis was evident as indicated by cellular and nuclear morphology and DNA fragmentation. Interestingly, pretreatment of SHSY-5Y cells with water-soluble Coenzyme Q10 (CoQ10) before paraquat exposure inhibited ROS generation. Pretreatment with CoQ10 also significantly reduced the number of apoptotic cells and DNA fragmentation. We also analyzed the effect of paraquat and CoQ10 on isolated mitochondria. Our results indicated that treatment with paraquat induced the generation of ROS from isolated mitochondria and depolarization of the inner mitochondrial membrane. Pretreatment with CoQ10 was able to inhibit ROS generation from isolated mitochondria as well as the collapse of mitochondrial membrane potential. Our results indicate that water-soluble CoQ10 can prevent oxidative stress and neuronal damage induced by paraquat and therefore, can be used for the prevention and therapy of neurodegenerative diseases caused by environmental toxins.

Authors+Show Affiliations

Chemistry and Biochemistry, University of Windsor, Windsor, Ontario, Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15519605

Citation

McCarthy, S, et al. "Paraquat Induces Oxidative Stress and Neuronal Cell Death; Neuroprotection By Water-soluble Coenzyme Q10." Toxicology and Applied Pharmacology, vol. 201, no. 1, 2004, pp. 21-31.
McCarthy S, Somayajulu M, Sikorska M, et al. Paraquat induces oxidative stress and neuronal cell death; neuroprotection by water-soluble Coenzyme Q10. Toxicol Appl Pharmacol. 2004;201(1):21-31.
McCarthy, S., Somayajulu, M., Sikorska, M., Borowy-Borowski, H., & Pandey, S. (2004). Paraquat induces oxidative stress and neuronal cell death; neuroprotection by water-soluble Coenzyme Q10. Toxicology and Applied Pharmacology, 201(1), 21-31.
McCarthy S, et al. Paraquat Induces Oxidative Stress and Neuronal Cell Death; Neuroprotection By Water-soluble Coenzyme Q10. Toxicol Appl Pharmacol. 2004 Nov 15;201(1):21-31. PubMed PMID: 15519605.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Paraquat induces oxidative stress and neuronal cell death; neuroprotection by water-soluble Coenzyme Q10. AU - McCarthy,S, AU - Somayajulu,M, AU - Sikorska,M, AU - Borowy-Borowski,H, AU - Pandey,S, PY - 2003/12/19/received PY - 2004/04/29/accepted PY - 2004/11/3/pubmed PY - 2004/12/22/medline PY - 2004/11/3/entrez SP - 21 EP - 31 JF - Toxicology and applied pharmacology JO - Toxicol. Appl. Pharmacol. VL - 201 IS - 1 N2 - Neuronal cell death induced by oxidative stress is correlated with numerous neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and stroke. The causes of sporadic forms of age-related neurodegenerative diseases are still unknown. Recently, a correlation between paraquat exposure and neurodegenerative diseases has been observed. Paraquat, a nonselective herbicide, was once widely used in North America and is still routinely used in Taiwan. We have used differentiated Human Neuroblastoma (SHSY-5Y) cells as an in vitro model to study the mechanism of cell death induced by paraquat. We observed that paraquat-induced oxidative stress in differentiated SHSY-5Y cells as indicated by an increase in the production of cellular reactive oxygen species (ROS). Furthermore, apoptosis was evident as indicated by cellular and nuclear morphology and DNA fragmentation. Interestingly, pretreatment of SHSY-5Y cells with water-soluble Coenzyme Q10 (CoQ10) before paraquat exposure inhibited ROS generation. Pretreatment with CoQ10 also significantly reduced the number of apoptotic cells and DNA fragmentation. We also analyzed the effect of paraquat and CoQ10 on isolated mitochondria. Our results indicated that treatment with paraquat induced the generation of ROS from isolated mitochondria and depolarization of the inner mitochondrial membrane. Pretreatment with CoQ10 was able to inhibit ROS generation from isolated mitochondria as well as the collapse of mitochondrial membrane potential. Our results indicate that water-soluble CoQ10 can prevent oxidative stress and neuronal damage induced by paraquat and therefore, can be used for the prevention and therapy of neurodegenerative diseases caused by environmental toxins. SN - 0041-008X UR - https://www.unboundmedicine.com/medline/citation/15519605/Paraquat_induces_oxidative_stress_and_neuronal_cell_death L2 - https://linkinghub.elsevier.com/retrieve/pii/S0041008X04002467 DB - PRIME DP - Unbound Medicine ER -