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Increasing CACNA1C expression in placenta containing high Cd level: an implication of Cd toxicity

  • Global pollution problems, Trends in Detection and Protection
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Abstract

Cadmium (Cd) has known to produce many adverse effects on organs including placenta. Many essential transporters are involved in Cd transport pathways such as DMT-1, ZIP as well as L-VDCC. Fourteen pregnant women participated and were divided into two groups: high and low Cd-exposed (H-Cd, L-Cd) groups on the basis of their residential areas, Cd concentrations in the blood (B-Cd), urine (U-Cd), and placenta (P-Cd). The results showed that the B-Cd and U-Cd were significantly increased in H-Cd group (p < 0.05). Interestingly, the P-Cd in H-Cd group was elevated (p < 0.05) and positively related to their B-Cd and U-Cd values (p < 0.05). However, the mean cord blood Cd (C-Cd) concentration in H-Cd group was not significantly increased about 2.5-fold when comparing to L-Cd group. To determine the Cd accumulation in placental tissues, metallothionein-1A (MT-1A) and metallothionein-2A (MT-2A) expressions were used as biomarkers. The results revealed that mean MT-1A and MT-2A mRNAs and MT-1/2 proteins were up-regulated in H-Cd group (p < 0.05). In addition, the Ca channel alpha 1C (CACNA1C) mRNA and protein expressions were noticeably elevated in H-Cd group (p < 0.05). From these findings, we suggested that CACNA1C might be implicated in Cd transport in human placenta.

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References

  • Belkacemi L, Bedard I, Simoneau L, Lafond J (2005) Calcium channels, transporters and exchangers in placenta: a review. Cell Calcium 37:1–8

    Article  CAS  Google Scholar 

  • Benoff S, Auborn K, Marmar JL, Hurley IR (2008) Link between low-dose environmentally relevant cadmium exposures and asthenozoospermia in a rat model. Fertil Steril 89:e73–e79

    Article  Google Scholar 

  • Berglund M, Akesson A, Nermell B, Vahter M (1994) Intestinal absorption of dietary cadmium in women depends on body iron stores and fiber intake. Environ Health Perspect 102:1058–1066

    Article  CAS  Google Scholar 

  • Bernard A (2008) Cadmium & its adverse effects on human health. Indian J Med Res 128:557–564

    CAS  Google Scholar 

  • Blazka ME, Shaikh ZA (1991) Differences in cadmium and mercury uptakes by hepatocytes: role of calcium channels. Toxicol Appl Pharmacol 110:355–363

    Article  CAS  Google Scholar 

  • Bush PG, Mayhew TM, Abramovich DR, Aggett PJ, Burke MD, Page KR (2000) A quantitative study on the effects of maternal smoking on placental morphology and cadmium concentration. Placenta 21:247–256

    Article  CAS  Google Scholar 

  • Chang X, Jin T, Chen L, Nordberg M, Lei L (2009) Metallothionein I isoform mRNA expression in peripheral lymphocytes as a biomarker for occupational cadmium exposure. Exp Biol Med 234:666–672

    Article  CAS  Google Scholar 

  • Cherian MG, Jayasurya A, Bay BH (2003) Metallothioneins in human tumors and potential roles in carcinogenesis. Mutat Res 533:201–209

    Article  CAS  Google Scholar 

  • Chiquoine AD (1965) Effect of cadmium chloride on the pregnant albino mouse. J Reprod Fertil 10:263–265

    Article  CAS  Google Scholar 

  • Davis SR, Cousins RJ (2000) Metallothionein expression in animals: a physiological perspective on function. J Nutr 130:1085–1088

    CAS  Google Scholar 

  • Donnelly L, Campling G (2008) Functions of the placenta. Anaesthesia & Intensive Care Medicine 9:124–127

    Article  Google Scholar 

  • Fernandez EL, Dencker L, Tallkvist J (2007) Expression of ZnT-1 (Slc30a1) and MT-1 (Mt1) in the conceptus of cadmium treated mice. Reprod Toxicol 24:353–358

    Article  CAS  Google Scholar 

  • Garrett SH, Somji S, Todd JH, Sens DA (1998) Exposure of human proximal tubule cells to cd2+, zn2+, and Cu2+ induces metallothionein protein accumulation but not metallothionein isoform 2 mRNA. Environ Health Perspect 106:587–595

    CAS  Google Scholar 

  • Gude NM, Roberts CT, Kalionis B, King RG (2004) Growth and function of the normal human placenta. Thromb Res 114:397–407

    Article  CAS  Google Scholar 

  • Henson MC, Chedrese PJ (2004) Endocrine disruption by cadmium, a common environmental toxicant with paradoxical effects on reproduction. Exp Biol Med (Maywood) 229:383–392

    CAS  Google Scholar 

  • Hinkle PM, Osborne ME (1994) Cadmium toxicity in rat pheochromocytoma cells: studies on the mechanism of uptake. Toxicol Appl Pharmacol 124:91–98

    Article  CAS  Google Scholar 

  • Hinkle PM, Kinsella PA, Osterhoudt KC (1987) Cadmium uptake and toxicity via voltage-sensitive calcium channels. J Biol Chem 262:16333–16337

    CAS  Google Scholar 

  • Ikeda M, Watanabe T, Ohashi F, Shimbo S (2010) Effects of variations in cadmium and lead levels in river sediments on local foods and body burden of local residents in non-polluted areas in Japan. Biol Trace Elem Res 133:255–264

    Article  CAS  Google Scholar 

  • Kantola M, Purkunen R, Kroger P, Tooming A, Juravskaja J, Pasanen M, Saarikoski S, Vartiainen T (2000) Accumulation of cadmium, zinc, and copper in maternal blood and developmental placental tissue: differences between Finland, Estonia, and St. Petersburg. Environ Res 83:54–66

    Article  CAS  Google Scholar 

  • Kippler M, Hoque AM, Raqib R, Ohrvik H, Ekstrom EC, Vahter M (2010) Accumulation of cadmium in human placenta interacts with the transport of micronutrients to the fetus. Toxicol Lett 192:162–168

    Article  CAS  Google Scholar 

  • Klaassen CD, Liu J, Choudhuri S (1999) Metallothionein: an intracellular protein to protect against cadmium toxicity. Annu Rev Pharmacol Toxicol 39:267–294

    Article  CAS  Google Scholar 

  • Knipp GT, Audus KL, Soares MJ (1999) Nutrient transport across the placenta. Adv Drug Deliv Rev 38:41–58

    Article  CAS  Google Scholar 

  • Lafond J, Simoneau L (2006) Calcium homeostasis in human placenta: role of calcium-handling proteins. Int Rev Cytol 250:109–174

    Article  CAS  Google Scholar 

  • Lauwerys RR, Bernard AM, Roels HA, Buchet JP (1994) Cadmium: exposure markers as predictors of nephrotoxic effects. Clin Chem 40:1391–1394

    CAS  Google Scholar 

  • Leazer T (2002) Cadmium absorption and its relationship to divalent metal transporter-1 in the pregnant rat. Toxicol Appl Pharmacol 185:18–24

    Article  CAS  Google Scholar 

  • Lin FJ, Fitzpatrick JW, Iannotti CA, Martin DS, Mariani BD, Tuan RS (1997) Effects of cadmium on trophoblast calcium transport. Placenta 18:341–356

    Article  CAS  Google Scholar 

  • Lu J, Jin T, Nordberg G, Nordberg M (2005) Metallothionein gene expression in peripheral lymphocytes and renal dysfunction in a population environmentally exposed to cadmium. Toxicol Appl Pharmacol 206:150–156

    Article  CAS  Google Scholar 

  • Mcaleer MF, Tuan RS (2001) Metallothionein overexpression in human trophoblastic cells protects against cadmium-induced apoptosis. In Vitr. Mol Toxicol 14:25–42

    Article  CAS  Google Scholar 

  • Min KS, Ueda H, Tanaka K (2008) Involvement of intestinal calcium transporter 1 and metallothionein in cadmium accumulation in the liver and kidney of mice fed a low-calcium diet. Toxicol Lett 176:85–92

    Article  CAS  Google Scholar 

  • Moreau R, Hamel A, Daoud G, Simoneau L, Lafond J (2002) Expression of calcium channels along the differentiation of cultured trophoblast cells from human term placenta. Biol Reprod 67:1473–1479

    Article  CAS  Google Scholar 

  • Nakamura Y, Ohba K, Ohta H (2012) Participation of metal transporters in cadmium transport from mother rat to fetus. J Toxicol Sci 37:1035–1044

    Article  CAS  Google Scholar 

  • Olsson IM, Bensryd I, Lundh T, Ottosson H, Skerfving S, Oskarsson A (2002) Cadmium in blood and urine—impact of sex, age, dietary intake, iron status, and former smoking-association of renal effects. Environ Health Perspect 110:1185–1190

    Article  CAS  Google Scholar 

  • Osman K, Akesson A, Berglund M, Bremme K, Schutz A, Ask K, Vahter M (2000) Toxic and essential elements in placentas of Swedish women. Clin Biochem 33:131–138

    Article  CAS  Google Scholar 

  • Ronco AM, Arguello G, Suazo M, Llanos MN (2005) Increased levels of metallothionein in placenta of smokers. Toxicology 208:133–139

    Article  CAS  Google Scholar 

  • Sabolic I, Breljak D, Skarica M, Herak-Kramberger CM (2010) Role of metallothionein in cadmium traffic and toxicity in kidneys and other mammalian organs. Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine 23:897–926

    Article  CAS  Google Scholar 

  • Sakulsak N (2012) Metallothionein: an overview on its metal homeostatic regulation in mammals. Int J Morphol 30:1007–1012

    Article  Google Scholar 

  • Salle BL, Senterre J, Glorieux FH, Delvin EE, Putet G (1987) Vitamin D metabolism in preterm infants. Biol Neonate 52(Suppl 1):119–130

    Article  CAS  Google Scholar 

  • Samarawickrama GP, Webb M (1979) Acute effects of cadmium on the pregnant rat and embryo-fetal development. Environ Health Perspect 28:245–249

    Article  CAS  Google Scholar 

  • Satarug S, Baker JR, Urbenjapol S, Haswell-Elkins M, Reilly PE, Williams DJ, Moore MR (2003) A global perspective on cadmium pollution and toxicity in non-occupationally exposed population. Toxicol Lett 137:65–83

    Article  CAS  Google Scholar 

  • Simmons RW, Pongsakul P, Saiyasitpanich D, Klinphoklap S (2005) Elevated levels of cadmium and zinc in paddy soils and elevated levels of cadmium in rice grain downstream of a zinc mineralized area in Thailand: implications for public health. Environ Geochem Health 27:501–511

    Article  CAS  Google Scholar 

  • Sorkun HC, Bir F, Akbulut M, Divrikli U, Erken G, Demirhan H, Duzcan E, Elci L, Celik I, Yozgatli U (2007) The effects of air pollution and smoking on placental cadmium, zinc concentration and metallothionein expression. Toxicology 238:15–22

    Article  CAS  Google Scholar 

  • Souza V, Bucio L, Gutierrez-Ruiz MC (1997) Cadmium uptake by a human hepatic cell line (WRL-68 cells). Toxicology 120:215–220

    Article  CAS  Google Scholar 

  • Swaddiwudhipong W, Limpatanachote P, Mahasakpan P, Krintratun S, Padungtod C (2007) Cadmium-exposed population in Mae Sot District, Tak Province: 1 prevalence of high urinary cadmium levels in the adults. J Med Assoc Thail 90:143–148

    Google Scholar 

  • Tsukahara T, Ezaki T, Moriguchi J, Furuki K, Shimbo S, Matsuda-Inoguchi N, Ikeda M (2003) Rice as the most influential source of cadmium intake among general Japanese population. Sci Total Environ 305:41–51

    Article  CAS  Google Scholar 

  • Wang L, Chen D, Wang H, Liu Z (2009) Effects of lead and/or cadmium on the expression of metallothionein in the kidney of rats. Biol Trace Elem Res 129:190–199

    Article  CAS  Google Scholar 

  • Zalups RK, Ahmad S (2003) Molecular handling of cadmium in transporting epithelia. Toxicol Appl Pharmacol 186:163–188

    Article  CAS  Google Scholar 

Download references

Acknowledgments

We are grateful for the Commission on Higher Education (CHE) funding under the Strategic Scholarships for Frontier Research Network for the Joint Ph.D. Program and the National Research Council of Thailand (NRCT). Additionally, we would like to express our sincere thanks to Dr. Witaya Swaddiwudhipong and staffs of Mae Sot General Hospital for the collaboration and sample collection as well as Mr. Ekarin Chulikorn for the kind suggestion. Finally, we appreciate for granting us the facility of the Faculty of Medical Science and Graduate school, Naresuan University.

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Authors and Affiliations

  1. Department of Anatomy, Faculty of Medical Science, Naresuan University, Phitsanulok, 65000, Thailand

    Laorrat Phuapittayalert, Phisid Saenganantakarn & Natthiya Sakulsak

  2. Department of Anatomy, School of Medical Science, University of Phayao, Phayao, 56000, Thailand

    Laorrat Phuapittayalert

  3. Department of Biochemistry, Faculty of Medical Science, Naresuan University, Phitsanulok, 65000, Thailand

    Wisa Supanpaiboon

  4. Department of Public Health, Faculty of Science, Buriram Rajabhat University, Buriram, 31000, Thailand

    Supaporn Cheunchoojit

  5. Department of Anatomy, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40000, Thailand

    Wiphawi Hipkaeo

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  1. Laorrat Phuapittayalert
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  2. Phisid Saenganantakarn
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  3. Wisa Supanpaiboon
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  6. Natthiya Sakulsak
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Correspondence to Natthiya Sakulsak.

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Phuapittayalert, L., Saenganantakarn, P., Supanpaiboon, W. et al. Increasing CACNA1C expression in placenta containing high Cd level: an implication of Cd toxicity. Environ Sci Pollut Res 23, 24592–24600 (2016). https://doi.org/10.1007/s11356-016-7841-4

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  • DOI: https://doi.org/10.1007/s11356-016-7841-4

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