Abstract
Exposure to the environmental pollutant lead (Pb) has been linked to Alzheimer’s disease (AD), in which mitochondrial dysfunction is a pathological consequence of neuronal degeneration. The toxicity of Pb in combination with β-amyloid peptides (1–40) and (25–35) causes selective death in neuronal cells. However, the precise mechanism through which Pb induces Alzheimer’s disease, particularly mitochondrial damage, is unknown. Changes in mitochondrial mass, membrane potential, mitochondrial complex activities, mitochondrial DNA and oxidative stress were examined in neuronal cells of human origin exposed to Pb and β-amyloid peptides (1–40) and (25–35) individually and in different combinations. The results showed depolarization of mitochondrial membrane potential, decrease in mitochondrial mass, ATP levels and mtDNA copy number in Pb and β-amyloid peptides (1–40) and (25–35) exposed cells. Also, significant reductions in the expression of mitochondrial electron transport chain (ETC) complex proteins (ATP5A, COXIV, UQCRC2, SDHB, NDUFS3), as well as down regulation of ETC complex gene expressions such as COXIV, ATP5F1 and NDUFS3 and antioxidant gene expressions like MnSOD and Gpx4 were observed in exposed cells. Furthermore, Pb and β-amyloid peptides exposure resulted in elevated mitochondrial malondialdehyde levels and a decrease in mitochondrial GSH levels. Our findings suggest that Pb toxicity could be one of the causative factors for the mitochondrial dysfunction and oxidative stress in Alzheimer’s disease progression.
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Data availability
The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.
Abbreviations
- Pb:
-
Lead
- AD:
-
Alzheimer’s disease
- Aβ:
-
Amyloid-beta
- MDA:
-
Malondialdehyde
- ROS:
-
Reactive oxygen species
- ETC:
-
Electron transport chain
- MMP:
-
Mitochondrial membrane potential
- ATP:
-
Adenosine triphosphate
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Acknowledgements
We thank the Indian Council of Medical Research (ICMR) for providing funds to carryout research and the University grants commission (UGC), Govt. of India for the award of the fellowship.
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This work has been supported by the grant 58/57/2012-BMS funded by Indian Council of Medical Research (ICMR).
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The entire work was completed by Lakshmi Jaya Madhuri Bandaru, who also wrote the manuscript and did the data analysis. Experiments were assisted by Lokesh Murumulla. The manuscript was edited and corrected by Krishna Prasad D and Bindu Lasya Challa. The project was created, revised, and managed by Suresh Challa.
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Bandaru, L.J.M., Murumulla, L., C., B.L. et al. Exposure of combination of environmental pollutant, lead (Pb) and β-amyloid peptides causes mitochondrial dysfunction and oxidative stress in human neuronal cells. J Bioenerg Biomembr 55, 79–89 (2023). https://doi.org/10.1007/s10863-023-09956-9
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DOI: https://doi.org/10.1007/s10863-023-09956-9