Linear chain aldehydes evoke calcium responses in B16 melanoma cells

Oxidative stress is involved in various physiological impairing stages, such as aging, diabetes, atherosclerosis, cirrhosis, and neurological disorders. Recent research indicates that aldehyde compounds derived from oxidized lipids increase in cancer patients compared to healthy individuals. Among of them, hexanal, a six-carbon liner chain aldehyde, is commonly found in cancer patients. Lipid oxidation products including aldehydes are in general chemically unstable and react with biological molecules such as proteins. The purpose of this study is to investigate effects of lipid-derived aldehydes and the related compounds on intracellular Ca²⁺ responses in B16 melanoma cells. Hexanal-induced [Ca²⁺]_i elevation is observed in B16 cells in a dose dependent manner, but [Ca²⁺]_i changes were observed neither in 3T3-L1 cells nor Caco-2 cells. Propanal, a chain length analogue of hexanal, elicited no change in [Ca²⁺]_i, but nonanal initiated [Ca²⁺]_i increases. Analogue compounds of hexanal failed to induce [Ca²⁺]_i elevation. Furthermore, unsaturated aldehydes known as TRPA1 channel agonists also failed to alter [Ca²⁺]_i levels in B16 melanoma cells. Pharmacological spectra using inhibitors against intracellular Ca²⁺ signaling suggest that hexanal-induced [Ca²⁺]_i responses in B16 cells might be involved in TRP channels other than TRPA1. Our results suggest that saturated aliphatic chain aldehydes would be novel compounds for initiating [Ca²⁺]_i increases through very strict recognitions of chain saturation, aldehydic base structures, and chain lengths in B16 melanoma cells. B16 cells would have sensing mechanisms for oxidative status and/or metabolic activities in their growth environment.