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Nickel and cadmium-induced SLBP depletion: A potential pathway to metal mediated cellular transformation
Ashley Jordan1,2, Xiaoru Zhang1, Jinquan Li3
1Department of Environmental Medicine, New York University School of Medicine, Tuxedo, New York, United States of America.
Abstract:
Both nickel and cadmium compounds have been established as group I carcinogens for several decades. Despite over-whelming evidence of these compounds' carcinogenicity in humans, the specific underlying molecular mechanisms that govern metal induced cellular transformation remain unclear. In this study, we found that there were slightly different effects on decreased SLBP mRNA and protein as well as increased polyA H3.1 in our nickel exposed cells. This suggested that nickel and arsenic have similar effects on canonical histone mRNA transcription and translation. We also saw that the depletion of SLBP protein was reversed by inhibiting the proteosome. Finally, we showed that inhibiting the SLBP mRNA and protein levels were rescued by epigenetic modifiers suggesting that nickel's effects on SLBP may be mediated via epigenetic mechanisms. Taken together these results suggest a similar mechanism by which both arsenic and nickel may exert their carcinogenic effects.
Insights
Nickel and arsenic exposure may cause cancer through similar molecular pathways. This study found nickel affects SLBP (stem-loop binding protein) via epigenetic mechanisms, potentially explaining its carcinogenicity.
Area of Science:
- Environmental toxicology
- Molecular carcinogenesis
- Epigenetics
Background:
- Nickel and cadmium are Group I carcinogens with unclear molecular mechanisms of action.
- Understanding metal-induced cellular transformation is crucial for public health.
Purpose of the Study:
- To investigate the molecular mechanisms underlying nickel-induced cellular transformation.
- To compare the effects of nickel and arsenic on gene expression and protein levels.
Main Methods:
- Exposure of cells to nickel compounds.
- Analysis of SLBP (stem-loop binding protein) mRNA and protein levels.
- Investigation of polyadenylated histone H3.1 (polyA H3.1) expression.
- Inhibition of the proteasome and epigenetic modifiers.
Main Results:
- Nickel exposure led to decreased SLBP mRNA and protein, and increased polyA H3.1.
- Nickel and arsenic exhibited similar effects on canonical histone mRNA transcription and translation.
- Proteasome inhibition reversed SLBP protein depletion.
- Epigenetic modifiers rescued SLBP mRNA and protein levels, suggesting epigenetic mediation.
Conclusions:
- Nickel's carcinogenic effects may be mediated through epigenetic mechanisms affecting SLBP.
- Nickel and arsenic share similar molecular pathways in exerting carcinogenic effects.
