Environmental Analysis Health and Toxicology

환경독성보건학회 (The Korean Society of Environmental Health and Toxicology)
권호 표지

테스토스테론생성 레이디히세포(Leydig)에서의 메탈로치오닌 유전자 발현특성연구

Expression of Metallothionein mRNA in Cadmium Treated Leydig Cells

  • 박광식 (동덕여자대학교 약학대학)
  • 발행 : 2004.09.01
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Although the biological functions of metallothioneins (MTs) are still being investigated, they have been suggested to be involved in detoxification of heavy metals, scavenging of free radicals, and protection against alkylating agents. MTs have been reported to be induced in most of animal tissues by heavy metals such as zinc, copper, mercury and cadmium, and the proteins have binding affinities to the metals. However, the presence or induction of MTs was reported not to be clear in leydig cells, which produce testosterone for the maturation of spermatozoa in male testes. In this study, we investigated the inducibility of metallothionein isomers by cadmium in cultured mouse leydig cells. Total RNA was extracted from the near confluent grown leydig cells and RT-PCR was Performed using the Primers which were synthesized on the basis of MT-1, 2, 3 and 4 cDNA from GenBank database. As results, MT-1 and MT-2 mRNA were found to be expressed in cadmium non-treated control cells and MT 1 mRNA expression was dose-dependent when leydig cells were treated with cadmium chloride. But MT-3 which is known to be brain specific and MT-4 which is another isoform of metallothionein, were not expressed. Other genes induced or depressed in cadmium treated leydig cells were also identified by microarray techniques.

키워드

참고문헌

  1. Abel J, Ruiter N and Kuhn-Velten W. Comparative study on metallothionein induction in whole testicular tissue and isolated leydig cells. 1991; 65: 228-234
  2. Afshari CA, Nuwaysir EF and Barrett JC, Application of complementary DNA microarray technology to carcinogen identification, toxicology, and drug safety evaluation. Can. Res. 1999; 59: 4759-4760
  3. Baker TK, Carfagna MA, Gao H, Dow ER, Li Q, Searfoss GH and TP. Ryan, Temporal gene expression analysis of monolayer cultured rat hepatocytes. Chem. Res. Toxicol. 2001: 14: 1218-1231 https://doi.org/10.1021/tx015518a
  4. Bunger J, Muller MM, Krahl J, Baum K, Weigel A, Hallier E and Schulz TG. Mutagenecity of diesel exhaust particles from two fossil and two plant oil fuels. Mutagenesis 2000; 15(5): 391-397 https://doi.org/10.1093/mutage/15.5.391
  5. Burczynski ME, McMillian M, Ciervo J, Li L, Parker JB, Dunn RT, Hicken S, Farr S and Johnson MD. Toxicogenomics-based discrimination of toxic mechanism in HepG2 human hepatoma cells. Toxicological Sci. 2000; 58: 399-415 https://doi.org/10.1093/toxsci/58.2.399
  6. Carero A, Hoet PH, Cerschaee L, Schoeters G and Nernery B. Genotoxic effects of carbon black particles, diesel exhaust particles, and urban air particulates and their extracts on a human alveolar epithelial cell line(A549) and a human monocytic cell line(THP-1). Environ Mol. Mutagen. 2001; 37(2): 155-163 https://doi.org/10.1002/em.1023
  7. Coyle P, Philcox, JC, Carey LC and Rofe AM. Metallothionein: The multipurpose protein. Cellular and Molecular Life Science. 2002; 59: 627-647 https://doi.org/10.1007/s00018-002-8454-2
  8. Gardmo C, H Swedlow and A Mode. Growth hormone regulation of rat liver gene expression assessed by SSH and microarray. Mol Cell. Endocrinol. 2002; 190: 125-133 https://doi.org/10.1016/S0303-7207(02)00004-7
  9. Gong, Q and Hart BA. Effect of thiols on cadmium induced expression of metallothionein and other oxidant stress genes in rat lung epithelial cells, Toxicology 1997; 119: 179-191 https://doi.org/10.1016/S0300-483X(96)03608-6
  10. Haider SG. Cell biology of leydig cells in the testis. Int. Rev. Cytol. 2004; 233: 181-241 https://doi.org/10.1016/S0074-7696(04)33005-6
  11. IARC. Beryllium, Cadmium, Mercury and Exposure in the glass manufacturing Industry. IARC Monograph on the evaluation of carcinogenic risk to humans. 1993; Vol 58, pp.119-238
  12. Koike ES, Hirano N, Shimojo and K Takahiro. cDNA microarray analysis of gene expression in rat alveolar macrophages in response to organic extract of diesel exhaust particles. Toxicol. Sci. 2002; 67: 241-246 https://doi.org/10.1093/toxsci/67.2.241
  13. Lambert E, Kille P and Swaminathan R. Cloning and sequencing a novel metallothionein I isoform expressed in human reticulocytes. FEBS Letters 1996; 389: 210-212 https://doi.org/10.1016/0014-5793(96)00587-X
  14. Lee C, Jeon SH, Na JG and Park K. Sequence analysis of choriogenin H gene of medaka (Oryzias latipes) and mRNA expression. Environ. Toxicol. Chem. 2002; 21(8): 1709-1714 https://doi.org/10.1897/1551-5028(2002)021<1709:SAOCHG>2.0.CO;2
  15. McKenna IM, Bare RM and Waalkes MP. Metallothionein gene expression in testicular interstitial cells and liver of rats treated with cadmium, Toxicology, 1996; 107: 120-130
  16. Nikuka H, Talonpoika T, Kaleva M and Toppari J. Inhibition of hCG-stimulated steroidogenesis in cultured leydig tumor cells by bisphenol A and octylphenols. Toxicol Appl Pharmacol. 1999; 157(3): 166-173 https://doi.org/10.1006/taap.1999.8674
  17. Nuwaysir EF, Bittner M, Trent J, Barret JC and Afshari CA. Microarrays Toxicology. The advent of toxicogenomics. Mol. Carcinogenesis, 1999; 24: 153-159 https://doi.org/10.1002/(SICI)1098-2744(199903)24:3<153::AID-MC1>3.0.CO;2-P
  18. Park K and Moon CK. Expression of metallothionien mRNA by diesel exhaust particles treated A549 cells. Kor, J. Env. Toxicol. 2004; 19(1): 59-64
  19. Park K and Koo JM. Expression of metallothionein in cadmium treated A549 cell line derived from human lung epithelial cells, Kor. J. Env. Toxicol. 2003; 18(1): 15-19
  20. Palmiter RD, Findley SD, Whitmore TE and Dumam DM. MT-III, a brain-specific member of the metallothionein gene family. Proc. Natl, Acad, Sci, USA, 1992; 89: 6333-6337 https://doi.org/10.1073/pnas.89.14.6333
  21. Pohjola SK, Lappi M, Honkanen M and Savela K. Comparison of mutagenicity and calf thymus DNA adducts formed by the particulate and semivolatile fractions of vehicle exhausts. Environ. Mol. Mutagen. 2003; 42(1): 26-36 https://doi.org/10.1002/em.10172
  22. Ren X, Zhou Y, Zhang J, Feng W and Jiao B. Metallothionein gene expression under different time in testicular sertoli and spermatogenic cells of rats treated with cadmium. Reproductive Toxicol. 2003; 17: 219-22 https://doi.org/10.1016/S0890-6238(02)00151-X
  23. Ryu J, Lee MS, Na JG, Chung K, Song BJ and Park K. Molecular cloning of cytochrome P4501A cDNA of medaka (Oryziase latipes) and messenger ribonucleinc acid regulation by environmenatl pollutants, Env. Toxicol and Chem 2004; 23(4): 1004-1011 https://doi.org/10.1897/03-27
  24. Schmidt CJ, Jubier MF and Harmer DH. Structure and expression of two human metallothionein-I isoform genes and a related pseudogene. J Biol. Chem. 1985; 260(12): 7731-7737
  25. Shin HJ, Park KK, Lee BH, Moon CK and Lee MO. Identification of genes that are induced after cadmium exposure by suppression subtractive hybridization. Toxicol. 2003;191: 121-131 https://doi.org/10.1016/S0300-483X(03)00210-5
  26. Shiraishi N, Hochadel JF, Coogan TP, Koropatnick J and Waalkes MP. Sensitivity to cadmium-induced genotoxicity in rat testicular cells is associated with minimal expression of the metallothionein gene. Toxicol. Appl. Pharmacol, 1995; 130: 229-236 https://doi.org/10.1006/taap.1995.1028
  27. Song KH, Lee K and Choi HS. Endocrine disrupter bisphenol A induces orphan nuclear receptor Nur 77 gene exression and steroidogenesis in mouse testicular leydig cells, 2002; 143(6): 2208-2215
  28. Tsangaris GT, A Botsonis, I Politis and F Tzorzatou-Stathopoulou. Evaluation of cadmium-induced transcriptome alterations by three color cDNA labeling microarray analysis on a T-cell line. Toxicology, 2002; 178: 135-160 https://doi.org/10.1016/S0300-483X(02)00236-6
  29. Wang S, Chen J and Lin L. Functional integrity of metallothionein genes in testicular cell lines, J. Cellular Biochem. 1994; 55: 486-496 https://doi.org/10.1002/jcb.240550408
  30. Yamada H and S. Koizum. DNA microarray analysis of human gene expression induced by a non-lethal dose of cadmium, Industrial Health, 2002; 40: 159-166 https://doi.org/10.2486/indhealth.40.159