The role of calcium, Akt and ERK signaling in cadmium-induced hair cell death

Galdieri, J.; Adams, C.; Stawicki, Tamara M.; Padilla, M.

The role of calcium, Akt and ERK signaling in cadmium-induced hair cell death

Abstract

Exposure to heavy metals has been shown to cause damage to a variety of different tissues and cell types including hair cells, the sensory cells of our inner ears responsible for hearing and balance. Elevated levels of one such metal, cadmium, have been associated with hearing loss and shown to cause hair cell death in multiple experimental models. While the mechanisms of cadmium-induced cell death have been extensively studied in other cell types they remain relatively unknown in hair cells. We have found that calcium signaling, which is known to play a role in cadmium-induced cell death in other cell types through calmodulin and CaMKII activation as well as IP3 receptor and mitochondrial calcium uniporter mediated calcium flow, does not appear to play a significant role in cadmium-induced hair cell death. While calmodulin inhibition can partially protect hair cells this may be due to impacts on mechanotransduction activity. Removal of extracellular calcium, and inhibiting CaMKII, the IP3 receptor and the mitochondrial calcium uniporter all failed to protect against cadmium-induced hair cell death. We also found cadmium treatment increased pAkt levels in hair cells and pERK levels in supporting cells. This activation may be protective as inhibiting these pathways enhances cadmiuminduced hair cell death rather than protecting cells. Thus cadmium-induced hair cell death appears distinct from cadmium-induced cell death in other cell types where calcium, Akt and ERK signaling all promote cell death.

Title	The role of calcium, Akt and ERK signaling in cadmium-induced hair cell death
Creator	Galdieri, J.
	Adams, C.
	Stawicki, Tamara M.
	Padilla, M.
Publisher	Molecular and Cellular Neuroscience
Academic Department	Neuroscience
Division	Natural Sciences
Organization	Lafayette College
Date Issued	March 2023
Date Available	2023-03-23
Type	Article
Language	English
Keyword	Akt
	Hair cells
	Calcium signaling
	Ototoxicity
	Cadmium
	ERK
Bibliographic Citation	Galdieri, J., et al. (2023 Mar) "The role of calcium, Akt and ERK signaling in cadmium-induced hair cell death." Molecular and Cellular Neuroscience 124: 103815.
Standard Identifier	DOI 10.1016/j.mcn.2023.103815
Standard Identifier	Handle 10385/9c67wp17f
Permalink	http://hdl.handle.net/10385/9c67wp17f
Rights Statement	Creative Commons - Attribution
Rights Holders	Adams, C.
	Stawicki, Tamara M.
	Padilla, M.
	Galdieri, J.