Abstract
Hair cells are sensitive to many insults including environmental toxins such as heavy metals. We show here that cadmium can consistently kill hair cells of the zebrafish lateral line. Disrupting hair cell mechanotransduction genetically or pharmacologically significantly reduces the amount of hair cell death seen in response to cadmium, suggesting a role for mechanotransduction in this cell death process, possibly as a means for cadmium uptake into the cells. Likewise, when looking at multiple cilia-associated gene mutants that have previously been shown to be resistant to aminoglycoside-induced hair cell death, resistance to cadmium-induced hair cell death is only seen in those with mechanotransduction defects. In contrast to what was seen with mechanotransduction, significant protection was not consistently seen from other ions previously shown to compete for cadmium uptake into cells or tissue including zinc and copper. These results show that functional mechanotransduction activity is playing a significant role in cadmium-induced hair cell death.
Highlights
Hearing loss is one of the most common sensory disorders affecting upwards of 20% of Americans over the age of 12 (Lin et al, 2011; Goman and Lin, 2016)
We found that there was significantly less cadmium-induced hair cell death in these mutants at all doses tested though hair cell death was not eliminated at higher cadmium chloride doses (Figures 2A,B)
We show that cadmium can consistently cause hair cell death in the lateral line system of zebrafish larvae
Summary
Hearing loss is one of the most common sensory disorders affecting upwards of 20% of Americans over the age of 12 (Lin et al, 2011; Goman and Lin, 2016). One common cause of hearing loss is the death of sensory hair cells. This is a cause of vestibular dysfunction. Heavy metals are naturally occurring and while some are required in the body at trace levels, higher levels are often associated with toxicity. Other heavy metals, such as cadmium, have no known function or benefit to animals. Cadmium is used in batteries and some pigments and is produced as a by-product of zinc mining It can be released into the environment through industrial run-off from a variety of different sources including mine drainage water, sewage treatment plans, and hazardous waste sites (IARC, 2012). Working in certain industries comes with a risk of occupational exposure to cadmium, and nonoccupational exposures can occur through diet or smoking (Faroon et al, 2012)
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