An acetyl-L-carnitine switch on mitochondrial dysfunction and rescue in the metabolomics study on aluminum oxide nanoparticles.

Abstract

BACKGROUND:

Due to the wide application of engineered aluminum oxide nanoparticles and increased aluminum containing particulate matter suspending in air, exposure of human to nano-scale aluminum oxide nanoparticles (Al2O3 NPs) is becoming inevitable.

METHODS:

In the present study, RNA microarray coupled with metabolomics analysis were used to uncover mechanisms underlying cellular responses to Al2O3 NPs and imply the potential rescue.

RESULTS:

We found that Al2O3 NPs significantly triggered down-regulation of mitochondria-related genes located in complex I, IV and V, which were involved in oxidative phosphorylation and neural degeneration pathways, in human bronchial epithelial (HBE) cells. Subsequent cell- and animal- based assays confirmed that Al2O3 NPs caused mitochondria-dependent apoptosis and oxidative stress either in vitro or in vivo, which were consistent with the trends of gene regulation. To rescue the Al2O3 NPs induced mitochondria dysfunction, disruption of small molecular metabolites of HBE were profiled using metabolomics analysis, which facilitates identification of potential antagonizer or supplement against nanoparticle-involved damages. Supplementation of an antioxidant, acetyl-L-carnitine, completely or partially restored the Al2O3 NPs modulated gene expression levels in mitochondrial complex I, IV and V. It further reduced apoptosis and oxidative damages in both Al2O3 NPs treated HBE cells and animal lung tissues.

CONCLUSION:

Thus, our results demonstrate the potential mechanism of respiratory system damages induced by Al2O3 NPs. Meanwhile, based on the metabolomics profiling, application of acetyl-L-carnitine is suggested to ameliorate mitochondria dysfunction associated with Al2O3 NPs.

• Authors: Xiaobo Li, Chengcheng Zhang, Xin Zhang, Shizhi Wang, Qingtao Meng, Shenshen Wu, Hongbao Yang, Yankai Xia, Rui Chen
• Journal: Particle and fibre toxicology (Part Fibre Toxicol) Vol. 13 Pg. 4 (Jan 16 2016) ISSN: 1743-8977 [Electronic] England
• PMID: 26772537 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants
• complex V (mitochondrial oxidative phosphorylation system)
• Acetylcarnitine
• Electron Transport Complex IV
• Mitochondrial Proton-Translocating ATPases
• Electron Transport Complex I
• Aluminum Oxide

Topics

• Acetylcarnitine (metabolism, pharmacology)
• Aluminum Oxide (toxicity)
• Animals
• Antioxidants (pharmacology)
• Apoptosis (drug effects)
• Cell Line
• Cytoprotection
• Dose-Response Relationship, Drug
• Electron Transport Complex I (genetics, metabolism)
• Electron Transport Complex IV (genetics, metabolism)
• Female
• Gene Expression Profiling (methods)
• Humans
• Lung (drug effects, metabolism, pathology)
• Lung Injury (chemically induced, genetics, metabolism, pathology, prevention & control)
• Male
• Metabolomics (methods)
• Metal Nanoparticles
• Mice, Inbred ICR
• Mitochondria (drug effects, metabolism, pathology)
• Mitochondrial Proton-Translocating ATPases (genetics, metabolism)
• Nanotechnology (methods)
• Nerve Degeneration
• Oligonucleotide Array Sequence Analysis
• Oxidative Phosphorylation
• Oxidative Stress (drug effects)
• Time Factors