Effects of lead and lead–melatonin exposure on protein and gene expression of metal transporters, proteins and the copper/zinc ratio in rats
- 151 Downloads
Human lead (Pb) exposure induces many adverse health effects, including some related to lead accumulation in organs. Although lead bio-distribution in the body has been described, the molecular mechanism underlying distribution and excretion is not well understood. The transport of essential and toxic metals is principally mediated by proteins. How lead affects the expression of metal transporter proteins in the principal metal excretory organs, i.e., the liver and kidney, is unknown. Considering that co-administration of melatonin and lead reduces the toxic effects of lead and lead levels in the blood in vivo, we examined how lead and co-administration of lead and melatonin affect the gene and protein expression of metal transporter proteins (ZIP8, ZIP14, CTR1 and DMT1) in these organs. Rats were exposed intraperitoneally to lead or lead-melatonin. Our results show that Pb exposure induces changes in the protein and gene expression of ZIP8, ZIP14 and CTR1. Alterations in the copper/zinc ratio found in the blood, liver and kidney were likely related to these changes. With DMT1 expression (gene and protein), a positive correlation was found with lead levels in the kidney. Co-administration of melatonin and lead reduced lead-induced DMT1 expression through an unknown mechanism. This effect of melatonin relates to reduced lead levels in the blood and kidney. The metal transport protein function and our results suggest that DMT1 likely contributes to lead accumulation in organs. These data further elucidate the effects of lead on Cu and Zn and the molecular mechanism underlying lead bio-distribution in animals.
KeywordsPb exposure DMT1 ZIP8 ZIP14 CTR1 Cu/Zn ratio Melatonin
Divalent metal transporter 1
Zinc transporter protein 14
Zinc transporter protein 8
Copper transporter 1
The authors thank Juan Pedro Galván, Dr. Martín Garcia, and Evelyn Flores for technical assistance. This work was partially supported by CONACYT (Grant CB-2011/0168474) and the Universidad de Guanajuato (Grant 2015-21 Excellency DAIP Funding).
- Galvez-Peralta M, Wang Z, Bao S, Knoell DL, Nebert DW (2014) Tissue-specific induction of mouse ZIP8 and ZIP14 divalent cation/bicarbonate symporters by, and cytokine response to inflammatory signals. Int J Toxicol 33:246–258. https://doi.org/10.1177/1091581814529310 CrossRefPubMedPubMedCentralGoogle Scholar
- Lichten LA, Liuzzi JP, Cousins RJ (2009) Interleukin-1beta contributes via nitric oxide to the upregulation and functional activity of the zinc transporter Zip14 (Slc39a14) in murine hepatocytes. Am J Physiol Gastrointest Liver Physiol 296:G860–G867. https://doi.org/10.1152/ajpgi.90676.2008 CrossRefPubMedPubMedCentralGoogle Scholar
- Martinez-Alfaro M, Hernandez-Cortes D, Wrobel K, Cruz-Jimenez G, Rivera-Leyva JC, Pina-Zentella RM, Carabez Trejo A (2012) Effect of melatonin administration on DNA damage and repair responses in lymphocytes of rats subchronically exposed to lead. Mutat Res 742:37–42. https://doi.org/10.1016/j.mrgentox.2011.11.011 CrossRefPubMedGoogle Scholar
- Martinez-Alfaro M, Ramirez-Garcia G, Gutierrez-Granados S, Alcaraz-Contreras Y, Gallegos-Corona MA, de Larrea GZ, Carabez-Trejo A (2013) Melatonin attenuates the effects of sub-acute administration of lead on kidneys in rats without altering the lead-induced reduction in nitric oxide. J Trace Elem Med Biol 27:364–369. https://doi.org/10.1016/j.jtemb.2013.05.003 CrossRefPubMedGoogle Scholar