Zinc adaptation and resistance to cadmium toxicity in mammalian cells: Molecular insight by proteomic analysis

Abstract

To identify proteins involved in cellular adaptive responses to zinc, a comparative proteome analysis between a previously developed high zinc- and cadmium-resistant human epithelial cell line (high zinc-resistant HeLa cells, HZR) and the parental HeLa cells has been carried out. Differentially produced proteins included cochaperones, proteins associated with oxido-reductase activities, and ubiquitin. Biochemical pathways to which these proteins belong were probed for their involvement in the resistance of both cell lines against cadmium toxicity. Among ER stressors, thapsigargin sensitized HZR cells, but not HeLa cells, to cadmium toxicity more acutely than tunicamycin, implying that these cells heavily relied on proper intracellular calcium distribution. The similar sensitivity of both HeLa and HZR cells to inhibitors of the proteasome, such as MG-132 or lactacystin, excluded improved proteasome activity as a mechanism associated with zinc adaptation of HZR cells. The enzyme 4-hydroxyphenylpyruvate dioxygenase (HPPD) was overproduced in HZR cells as compared to HeLa cells. It transforms HPP to homogentisate in the second step of tyrosine catabolism. Inhibition of HPPD decreased the resistance of HZR cells against cadmium, but not that of HeLa cells, suggesting that adaptation to zinc overload and increased HPP removal are linked in HZR cells.

Comparative Proteomic Analysis of the Molecular Responses of Mouse Macrophages to Titanium Dioxide and Copper Oxide Nanoparticles Unravels Some Toxic Mechanisms for Copper Oxide Nanoparticles in Macrophages

“…Next, we tested whether the tetrahydrobiopterin-dependent amino acid hydroxylations could show an interplay with copper toxicity. As tyrosine has been shown to play a role in zinc resistance [ 78 ], the products of the amino acid hydroxylations, i.e. tyrosine, DOPA and 6-hydroxytryptophan were tested by adding them at non toxic doses together with varying copper concentrations.…”

Levels of Aqueous Humor Trace Elements in Patients with Non-Exsudative Age-related Macular Degeneration: A Case-control Study

“…This interaction is regularly observed in a variety of conditions [15]. Zinc often affords protection against cadmium toxicity, and cells adapted to high zinc concentrations display changed cellular handling homeostasis of cadmium, manganese, and calcium [16].…”

Sex Differences in Shotgun Proteome Analyses for Chronic Oral Intake of Cadmium in Mice

“…Proteomic studies related to acute cadmium poisoning have been performed on mice [ 20 , 21 ] cultured rat cells [ 38 – 40 ], mouse cells [ 41 , 42 ], and human cells [ 43 – 45 ], as well as other organisms [ 46 – 48 ]: The heat shock protein family, cytokeratin family, and Ube2d family were identified as up-regulated proteins. These findings obviously differ from the present results noted in chronic oral cadmium intake due to different pathological metabolism.…”