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Arsenic Induces Thioredoxin 1 and Apoptosis in Human Liver HHL-5 Cells
Yuanyuan Li1, Yuanyuan Zhang1, Yanhui Gao1
1Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Key Laboratory of Etiologic Epidemiology of Education Bureau of Heilongjiang Province and Ministry of Health, Harbin Medical University, Harbin, 150081, China.
Abstract:
To further characterize the mechanisms underlying liver toxicity induced by arsenic, we examined in this study the effect of arsenic on thioredoxin (Trx) and the apoptotic signaling pathways in human liver HHL-5 cells. The cells were treated with 0, 2, 5, and 10 μM of sodium arsenite for 24 h, and the changes of Trx1 and thioredoxin reductase (TrxR1) as well as intracellular ROS and apoptosis were examined. A concentration-dependent increase in mRNA and protein levels of Trx1 and TrxR1 was observed in arsenic-treated cells. Intracellular ROS levels and apoptosis were also significantly increased in a concentration-dependent manner. In line with this, protein levels of Bax and cytochrome C were increased and Bcl-2 was decreased by arsenic treatments. Increases in caspase 3 activity were observed. These results indicate that Trx is involved in arsenic-induced liver cell injury, probably through the apoptotic signaling pathway. However, further studies are needed to elucidate on these findings.
Insights
Arsenic exposure increases thioredoxin (Trx) and thioredoxin reductase (TrxR1) in liver cells. This arsenic-induced liver injury involves increased oxidative stress and apoptosis via the mitochondrial pathway.
Area of Science:
- Toxicology
- Cell Biology
- Biochemistry
Background:
- Arsenic is a known toxicant with significant health implications.
- Understanding the molecular mechanisms of arsenic-induced liver toxicity is crucial for developing effective interventions.
- The role of the thioredoxin system in cellular response to toxicants requires further elucidation.
Purpose of the Study:
- To investigate the effect of arsenic on the thioredoxin (Trx) system in human liver cells.
- To explore the involvement of apoptotic signaling pathways in arsenic-induced liver toxicity.
- To characterize the relationship between arsenic exposure, oxidative stress, and cell death.
Main Methods:
- Human liver HHL-5 cells were treated with varying concentrations of sodium arsenite (0-10 μM) for 24 hours.
- Quantitative analysis of Trx1 and TrxR1 mRNA and protein levels.
- Assessment of intracellular reactive oxygen species (ROS) levels, apoptosis markers (Bax, Bcl-2, cytochrome c), and caspase 3 activity.
Main Results:
- Arsenic treatment led to a concentration-dependent increase in both mRNA and protein levels of Trx1 and TrxR1.
- Significant, dose-dependent increases in intracellular ROS and apoptosis were observed.
- Arsenic altered the expression of apoptosis-related proteins (increased Bax and cytochrome c, decreased Bcl-2) and elevated caspase 3 activity.
Conclusions:
- The thioredoxin system is upregulated in response to arsenic exposure in liver cells.
- Arsenic induces liver cell injury likely through oxidative stress and activation of the intrinsic apoptotic pathway.
- These findings suggest a role for Trx in mediating arsenic-induced hepatotoxicity, warranting further investigation.
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