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Zinc supplementation protects against cadmium accumulation and cytotoxicity in Madin-Darby bovine kidney cells.

Zhang D, Liu J, Gao J, Shahzad M, Han Z, Wang Z, Li J, Sjölinder H - PLoS ONE (2014)

Bottom Line: Metallothioneins (MTs) are metal-binding proteins that play an essential role in heavy metal ion detoxification.We found that co-exposure to Zn2+ and Cd2+ synergistically enhanced RNA and protein expression of MT-1, MT-2, and the metal-regulatory transcription factor 1 in MDBK cells.Notably, addition of Zn2+ reduced the amounts of cytosolic Cd2+ detected following MDBK exposure to 10 μM Cd2+.

View Article: PubMed Central - PubMed

Affiliation: College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, PR China.

ABSTRACT
Cadmium ions (Cd2+) have been reported to accumulate in bovine tissues, although Cd2+ cytotoxicity has not been investigated thoroughly in this species. Zinc ions (Zn2+) have been shown to antagonize the toxic effects of heavy metals such as Cd2+ in some systems. The present study investigated Cd2+ cytotoxicity in Madin-Darby bovine kidney (MDBK) epithelial cells, and explored whether this was modified by Zn2+. Exposure to Cd2+ led to a dose- and time-dependent increase in apoptotic cell death, with increased intracellular levels of reactive oxygen species and mitochondrial damage. Zn2+ supplementation alleviated Cd2+-induced cytotoxicity and this protective effect was more obvious when cells were exposed to a lower concentration of Cd2+ (10 μM), as compared to 50 μM Cd2+. This indicated that high levels of Cd2+ accumulation might induce irreversible damage in bovine kidney cells. Metallothioneins (MTs) are metal-binding proteins that play an essential role in heavy metal ion detoxification. We found that co-exposure to Zn2+ and Cd2+ synergistically enhanced RNA and protein expression of MT-1, MT-2, and the metal-regulatory transcription factor 1 in MDBK cells. Notably, addition of Zn2+ reduced the amounts of cytosolic Cd2+ detected following MDBK exposure to 10 μM Cd2+. These findings revealed a protective role of Zn2+ in counteracting Cd2+ uptake and toxicity in MDBK cells, indicating that this approach may provide a means to protect livestock from excessive Cd2+ accumulation.

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Quantification of intracellular Cd2+ and Zn2+.MDBK cells were treated with 10 μM (A) or 50 μM (B) Cd2+, alone or in combination with Zn2+ (0, 10, or 50 μM). At the indicated time points, the intracellular levels of Zn2+ and Cd2+ (ng/1×104 cells) were determined by ICP-MS, as described in the Materials and Methods section. The results represent the mean ± SD (n = 4). *P<0.05, compared to the cells without Zn2+ supplementation.
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pone-0103427-g005: Quantification of intracellular Cd2+ and Zn2+.MDBK cells were treated with 10 μM (A) or 50 μM (B) Cd2+, alone or in combination with Zn2+ (0, 10, or 50 μM). At the indicated time points, the intracellular levels of Zn2+ and Cd2+ (ng/1×104 cells) were determined by ICP-MS, as described in the Materials and Methods section. The results represent the mean ± SD (n = 4). *P<0.05, compared to the cells without Zn2+ supplementation.

Mentions: As Zn2+ protected MDBK cells from Cd2+-induced cytotoxicity and up-regulated MT proteins, we next explored whether Zn2+ administration was able to reduce intracellular Cd2+ accumulation. MDBK cells were treated with 10 μM (Fig. 5A) or 50 μM (Fig. 5B) Cd2+ in the presence or absence of Zn2+ at indicated concentrations (0 to 50 μM), and the intracellular levels of Zn2+ and Cd2+ were determined over time using ICP-MS. In cells exposed to 10 μM Cd2+, addition of Zn2+ resulted in a dose-dependent reduction in the intracellular Cd2+ level, which was associated with increased levels of intracellular Zn2+ (Fig. 5A). In contrast, the inhibitory impact of Zn2+ supplementation on Cd2+ uptake was not obvious in cells exposed to a high concentration of Cd2+ (50 μM). Moreover, exposure to a high concentration of Zn2+ (50 μM) even tended to increase intracellular Cd2+ levels (Fig. 5B, right panel). Notably, the intracellular Zn2+ level under these circumstances was comparable to that of control samples after 24 h treatment, even though transient Zn2+ absorption was detected (Fig. 5B, left panel). These results indicated that Zn2+ supplementation was able to prevent Cd2+ uptake into MDBK cells, but its efficacy was dependent on the level of Cd2+ exposure.


Zinc supplementation protects against cadmium accumulation and cytotoxicity in Madin-Darby bovine kidney cells.

Zhang D, Liu J, Gao J, Shahzad M, Han Z, Wang Z, Li J, Sjölinder H - PLoS ONE (2014)

Quantification of intracellular Cd2+ and Zn2+.MDBK cells were treated with 10 μM (A) or 50 μM (B) Cd2+, alone or in combination with Zn2+ (0, 10, or 50 μM). At the indicated time points, the intracellular levels of Zn2+ and Cd2+ (ng/1×104 cells) were determined by ICP-MS, as described in the Materials and Methods section. The results represent the mean ± SD (n = 4). *P<0.05, compared to the cells without Zn2+ supplementation.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4126686&req=5

pone-0103427-g005: Quantification of intracellular Cd2+ and Zn2+.MDBK cells were treated with 10 μM (A) or 50 μM (B) Cd2+, alone or in combination with Zn2+ (0, 10, or 50 μM). At the indicated time points, the intracellular levels of Zn2+ and Cd2+ (ng/1×104 cells) were determined by ICP-MS, as described in the Materials and Methods section. The results represent the mean ± SD (n = 4). *P<0.05, compared to the cells without Zn2+ supplementation.
Mentions: As Zn2+ protected MDBK cells from Cd2+-induced cytotoxicity and up-regulated MT proteins, we next explored whether Zn2+ administration was able to reduce intracellular Cd2+ accumulation. MDBK cells were treated with 10 μM (Fig. 5A) or 50 μM (Fig. 5B) Cd2+ in the presence or absence of Zn2+ at indicated concentrations (0 to 50 μM), and the intracellular levels of Zn2+ and Cd2+ were determined over time using ICP-MS. In cells exposed to 10 μM Cd2+, addition of Zn2+ resulted in a dose-dependent reduction in the intracellular Cd2+ level, which was associated with increased levels of intracellular Zn2+ (Fig. 5A). In contrast, the inhibitory impact of Zn2+ supplementation on Cd2+ uptake was not obvious in cells exposed to a high concentration of Cd2+ (50 μM). Moreover, exposure to a high concentration of Zn2+ (50 μM) even tended to increase intracellular Cd2+ levels (Fig. 5B, right panel). Notably, the intracellular Zn2+ level under these circumstances was comparable to that of control samples after 24 h treatment, even though transient Zn2+ absorption was detected (Fig. 5B, left panel). These results indicated that Zn2+ supplementation was able to prevent Cd2+ uptake into MDBK cells, but its efficacy was dependent on the level of Cd2+ exposure.

Bottom Line: Metallothioneins (MTs) are metal-binding proteins that play an essential role in heavy metal ion detoxification.We found that co-exposure to Zn2+ and Cd2+ synergistically enhanced RNA and protein expression of MT-1, MT-2, and the metal-regulatory transcription factor 1 in MDBK cells.Notably, addition of Zn2+ reduced the amounts of cytosolic Cd2+ detected following MDBK exposure to 10 μM Cd2+.

View Article: PubMed Central - PubMed

Affiliation: College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, PR China.

ABSTRACT
Cadmium ions (Cd2+) have been reported to accumulate in bovine tissues, although Cd2+ cytotoxicity has not been investigated thoroughly in this species. Zinc ions (Zn2+) have been shown to antagonize the toxic effects of heavy metals such as Cd2+ in some systems. The present study investigated Cd2+ cytotoxicity in Madin-Darby bovine kidney (MDBK) epithelial cells, and explored whether this was modified by Zn2+. Exposure to Cd2+ led to a dose- and time-dependent increase in apoptotic cell death, with increased intracellular levels of reactive oxygen species and mitochondrial damage. Zn2+ supplementation alleviated Cd2+-induced cytotoxicity and this protective effect was more obvious when cells were exposed to a lower concentration of Cd2+ (10 μM), as compared to 50 μM Cd2+. This indicated that high levels of Cd2+ accumulation might induce irreversible damage in bovine kidney cells. Metallothioneins (MTs) are metal-binding proteins that play an essential role in heavy metal ion detoxification. We found that co-exposure to Zn2+ and Cd2+ synergistically enhanced RNA and protein expression of MT-1, MT-2, and the metal-regulatory transcription factor 1 in MDBK cells. Notably, addition of Zn2+ reduced the amounts of cytosolic Cd2+ detected following MDBK exposure to 10 μM Cd2+. These findings revealed a protective role of Zn2+ in counteracting Cd2+ uptake and toxicity in MDBK cells, indicating that this approach may provide a means to protect livestock from excessive Cd2+ accumulation.

Show MeSH
Related in: MedlinePlus