Sub-lethal concentrations of CdCl2 disrupt cell migration and cytoskeletal proteins in cultured mouse TM4 Sertoli cells. (April 2016)

• Record Type: Journal Article
• Authors: Egbowon, Biola F.; Harris, Wayne; Arnott, Gordon; Mills, Chris Lloyd; Hargreaves, Alan J.
• Is Part Of: Toxicology in vitro. Volume 32(2016)
• Page Start: 154
• Page End: 165
• Publication Date: 2016-04
• Subjects: AIDA Advanced Image Data Analyser -- BSA bovine serum albumin -- CdCl2 cadmium chloride -- CFSE carboxyfluorescein diacetate succinimidyl ester -- DAPI 4′, 6-diamidino-2-phenylindole -- DMSO dimethyl sulfoxide -- FITC fluorescein isothiocyanate -- H and E haematoxylin and eosin -- IC50 inhibiting concentration (50%) -- LDH lactate dehydrogenase -- MFs microfilaments -- MTs microtubules -- MTT 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide -- PBS phosphate buffered saline -- SDS sodium dodecyl sulphate -- TBS Tris-buffered saline -- 5-FU 5-fluorouracil; Cadmium chloride -- Sertoli cells -- Reproductive toxicity -- Cytoskeleton -- Cell migration -- Testicular development; Toxicity testing -- In vitro -- Periodicals; Toxicology -- Periodicals; 615.9
• DOI: 10.1016/j.tiv.2015.12.017
• Languages: English
• ISSNs: 0887-2333

Abstract

Abstract: The aims of this study were to examine the effects of CdCl2 on the viability, migration and cytoskeleton of cultured mouse TM4 Sertoli cells. Time- and concentration-dependent changes were exhibited by the cells but 1 μM CdCl2 was sub-cytotoxic at all time-points. Exposure to 1 and 12 μM CdCl2 for 4 h resulted in disruption of the leading edge, as determined by chemical staining. Cell migration was inhibited by both 1 and 12 μM CdCl2 in a scratch assay monitored by live cell imaging, although exposure to the higher concentration was associated with cell death. Western blotting and immunofluorescence staining indicated that CdCl2 caused a concentration dependent reduction in actin and tubulin levels. Exposure to Cd 2 + also resulted in significant changes in the levels and/or phosphorylation status of the microtubule and microfilament destabilising proteins cofilin and stathmin, suggesting disruption of cytoskeletal dynamics. Given that 1–12 μM Cd 2 + is attainable in vivo, our findings are consistent with the possibility that Cd 2 + induced impairment of testicular development and reproductive health may involve a combination of reduced Sertoli cell migration and impaired Sertoli cell viability depending on the timing, level and duration of exposure. Highlights: CdCl2 reduced cultured mouse TM4 Sertoli cell viability dose and time dependently. A sublethal level of 1 μM CdCl2 disrupted cell migration and the cytoskeleton. Similar effects were exerted by 12 μM CdCl2 but were associated with cell death. Such levels of Cd 2 + have been detected by others in human and rodent tissues. At these levels Cd 2 + may disrupt Sertoli cell migration and viability in vivo.