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Published on: May 2, 2020
Duration-dependent effects of nicotine exposure on growth and AKT activation in human kidney epithelial cells
Yu-Wei Chang1, Kamaleshwar P Singh2
1Department of Environmental Toxicology, The Institute of Environmental and Human Health (TIEHH), Texas Tech University, Lubbock, TX, 79409, USA.
Abstract:
Exposure to nicotine is known to cause adverse effects in many target organs including kidney. Epidemiological studies suggest that nicotine-induced kidney diseases are prevalent worldwide. However, the impact of duration of exposure on the nicotine-induced adverse effects in normal kidney cells and the underlying molecular mechanism is still unclear. Hence, the objective of this study was to evaluate both acute and long-term effects of nicotine in normal human kidney epithelial cells (HK-2). Cells were treated with 1 and 10 µM nicotine for acute and long-term duration. The result of cell viability showed that the acute exposure to 1 µM nicotine has no significant effect on growth. However, the 10 µM nicotine caused significant decrease in the growth of HK-2 cells. The long-term exposure resulted in significantly increased cell growth in both 1 and 10 µM nicotine-treated groups. Analysis of cell cycle and expression of marker genes related to proliferation and apoptosis further confirmed the effects of nicotine. Additionally, the analysis of growth signaling pathway revealed the decreased level of pAKT in cells with acute exposure whereas the increased level of pAKT in long-term nicotine-exposed cells. This suggests that nicotine, through modulating the AKT pathway, controls the duration-dependent effects on the growth of HK-2 cells. In summary, this is the first report showing long-duration exposure to nicotine causes increased proliferation of human kidney epithelial cells through activation of AKT pathway.
Insights
Nicotine exposure impacts kidney cells differently based on duration. Acute exposure can harm kidney cells, while long-term nicotine exposure promotes their proliferation via the AKT pathway.
Area of Science:
- Nephrology
- Toxicology
- Cell Biology
Background:
- Nicotine exposure is linked to adverse kidney effects globally.
- The impact of exposure duration on nicotine-induced kidney damage and its molecular mechanisms remain unclear.
Purpose of the Study:
- To investigate the acute and long-term effects of nicotine on normal human kidney epithelial cells (HK-2).
- To elucidate the molecular mechanisms underlying nicotine's duration-dependent effects on kidney cell growth.
Main Methods:
- HK-2 cells were treated with 1 and 10 µM nicotine for acute and long-term durations.
- Cell viability, cell cycle, apoptosis markers, and the AKT signaling pathway were analyzed.
Main Results:
- Acute exposure to 10 µM nicotine decreased cell viability, while 1 µM had no significant effect.
- Long-term exposure to both concentrations of nicotine significantly increased cell proliferation.
- Acute nicotine exposure decreased pAKT levels, whereas long-term exposure increased pAKT levels, indicating AKT pathway modulation.
Conclusions:
- Nicotine exhibits duration-dependent effects on human kidney epithelial cells.
- Long-term nicotine exposure promotes kidney cell proliferation by activating the AKT pathway.
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