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Protective Effects of PGC-1α Against Lead-Induced Oxidative Stress and Energy Metabolism Dysfunction in Testis Sertoli Cells

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Abstract

The reproductive system is sensitive to lead (Pb) toxicity, which has long been an area of research interest, but the underlying mechanisms remain to be illustrated. Peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is pivotal in mitochondrial function. In this study, mouse testis Sertoli cells (TM4 cells), PGC-1α lower-expression (PGC-1α(−)) TM4 cells and PGC-1α overexpression (PGC-1α(+)) TM4 cells were used to explore the protective roles of PGC-1α against lead toxicity on the mouse reproductive system. Lead acetate (PbAc) exposure decreased the expression level of PGC-1α, increased the intracellular level of reactive oxygen species (ROS), and reduced the level of ATP in the three TM4 cell lines. The effects of PbAc on intracellular ATP level and on ROS content were significantly weakened in PGC-1α(+)TM4 cells versus TM4 cells and were significantly amplified in PGC-1α(−)TM4 cells versus TM4 cells. These results suggest that PGC-1α is a protective factor against PbAc-induced oxidative stress and energy metabolism dysfunction in the mouse reproductive system, thereby holding the potential of being developed as a preventive or therapeutic strategy against disorders induced by lead exposure.

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Abbreviations

PbAc:

Lead acetate

TM4:

Mouse testis Sertoli cells

PGC-1α:

Peroxisome proliferator-activated receptor γ coactivator 1α

ROS:

Reactive oxygen species

LD:

Lactic acid

LDH:

Lactic dehydrogenase

SDH:

Succinate dehydrogenase

Reference

  1. Li X, Ye F, Li L, Chang W, Wu X, Chen J (2016) The role of HO-1 in protection against lead-induced neurotoxicity. Neurotoxicology 52:1–11. doi:10.1016/j.neuro.2015.10.015

    Article  PubMed  Google Scholar 

  2. Ye F, Li X, Li L, Lyu L, Yuan J, Chen J (2015) The role of Nrf2 in protection against Pb-induced oxidative stress and apoptosis in SH-SY5Y cells. Food Chem Toxicol 86:191–201. doi:10.1016/j.fct.2015.10.009

    Article  CAS  PubMed  Google Scholar 

  3. LH X, FF M, Zhao JH, He Q, Cao CL, Yang H, Liu Q, Liu XH, Sun SJ (2015) Lead induces apoptosis and histone hyperacetylation in rat cardiovascular tissues. PLoS One 10(6):e129091. doi:10.1371/journal.pone.0129091

    Google Scholar 

  4. Bellinger DC (2005) Teratogen update: lead and pregnancy. Birth Defects Res A Clin Mol Teratol 73(6):409–420. doi:10.1002/bdra.20127

    Article  CAS  PubMed  Google Scholar 

  5. Shen W, Chen J, Yin J, Wang SL (2016) Selenium protects reproductive system and foetus development in a rat model of gestational lead exposure. Eur Rev Med Pharmacol Sci 20(4):773–780

    CAS  PubMed  Google Scholar 

  6. Kasperczyk A, Dobrakowski M, Czuba ZP, Horak S, Kasperczyk S (2015) Environmental exposure to lead induces oxidative stress and modulates the function of the antioxidant defense system and the immune system in the semen of males with normal semen profile. Toxicol Appl Pharmacol 284(3):339–344. doi:10.1016/j.taap.2015.03.001

    Article  CAS  PubMed  Google Scholar 

  7. Oktem F, Arslan MK, Dundar B, Delibas N, Gultepe M, Ergurhan II (2004) Renal effects and erythrocyte oxidative stress in long-term low-level lead-exposed adolescent workers in auto repair workshops. Arch Toxicol 78(12):681–687. doi:10.1007/s00204-004-0597-5

    Article  PubMed  Google Scholar 

  8. Wang ZK, Zhou XL, Song XB, Zhuang DM, Wang ZY, Yang DB, Wang L (2016) Alleviation of lead-induced apoptosis by Puerarin via inhibiting mitochondrial permeability transition pore opening in primary cultures of rat proximal tubular cells. Biol Trace Elem Res. doi:10.1007/s12011-016-0701-8

    Google Scholar 

  9. Hsu PC, Guo YL (2002) Antioxidant nutrients and lead toxicity. Toxicology 180(1):33–44

    Article  CAS  PubMed  Google Scholar 

  10. Li N, Hou YH, Jing WX, Dahms HU, Wang L (2016) Quality decline and oxidative damage in sperm of freshwater crab Sinopotamon henanense exposed to lead. Ecotoxicol Environ Saf 130:193–198. doi:10.1016/j.ecoenv.2016.03.042

    Article  CAS  PubMed  Google Scholar 

  11. Dkhil MA, Moneim AE, Al-Quraishy S (2016) Indigofera Oblongifolia ameliorates lead acetate-induced testicular oxidative damage and apoptosis in a rat model. Biol Trace Elem Res. doi:10.1007/s12011-016-0689-0

    PubMed  Google Scholar 

  12. Lee NP, Cheng CY (2004) Adaptors, junction dynamics, and spermatogenesis. Biol Reprod 71(2):392–404. doi:10.1095/biolreprod.104.027268

    Article  CAS  PubMed  Google Scholar 

  13. Huang S, Ye J, Yu J, Chen L, Zhou L, Wang H, Li Z, Wang C (2014) The accumulation and efflux of lead partly depend on ATP-dependent efflux pump-multidrug resistance protein 1 and glutathione in testis Sertoli cells. Toxicol Lett 226(3):277–284. doi:10.1016/j.toxlet.2014.02.017

    Article  CAS  PubMed  Google Scholar 

  14. Kong X, Wang R, Xue Y, Liu X, Zhang H, Chen Y, Fang F, Chang Y (2010) Sirtuin 3, a new target of PGC-1alpha , plays an important role in the suppression of ROS and mitochondrial biogenesis. PLoS One 5(7):e11707. doi:10.1371/journal.pone.0011707

    Article  PubMed  PubMed Central  Google Scholar 

  15. Puigserver P, Wu Z, Park CW, Graves R, Wright M, Spiegelman BM (1998) A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell 92(6):829–839

    Article  CAS  PubMed  Google Scholar 

  16. Ahn BH, Kim HS, Song S, Lee IH, Liu J, Vassilopoulos A, Deng CX, Finkel T (2008) A role for the mitochondrial deacetylase Sirt3 in regulating energy homeostasis. Proc Natl Acad Sci U S A 105(38):14447–14452. doi:10.1073/pnas.0803790105

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Finley LW, Carracedo A, Lee J, Souza A, Egia A, Zhang J, Teruya-Feldstein J, Moreira PI, Cardoso SM, Clish CB, Pandolfi PP, Haigis MC (2011) SIRT3 opposes reprogramming of cancer cell metabolism through HIF1alpha destabilization. Cancer Cell 19(3):416–428. doi:10.1016/j.ccr.2011.02.014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Sparks LM, Xie H, Koza RA, Mynatt R, Hulver MW, Bray GA, Smith SR (2005) A high-fat diet coordinately downregulates genes required for mitochondrial oxidative phosphorylation in skeletal muscle. Diabetes 54(7):1926–1933

    Article  CAS  PubMed  Google Scholar 

  19. Jing E, Emanuelli B, Hirschey MD, Boucher J, Lee KY, Lombard D, Verdin EM, Kahn CR (2011) Sirtuin-3 (Sirt3) regulates skeletal muscle metabolism and insulin signaling via altered mitochondrial oxidation and reactive oxygen species production. Proc Natl Acad Sci U S A 108(35):14608–14613. doi:10.1073/pnas.1111308108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Lu Z, Xu X, Hu X, Fassett J, Zhu G, Tao Y, Li J, Huang Y, Zhang P, Zhao B, Chen Y (2010) PGC-1 alpha regulates expression of myocardial mitochondrial antioxidants and myocardial oxidative stress after chronic systolic overload. Antioxid Redox Signal 13(7):1011–1022. doi:10.1089/ars.2009.2940

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Bell EL, Guarente L (2011) The SirT3 divining rod points to oxidative stress. Mol Cell 42(5):561–568. doi:10.1016/j.molcel.2011.05.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Finkel T, Deng CX, Mostoslavsky R (2009) Recent progress in the biology and physiology of sirtuins. Nature 460(7255):587–591. doi:10.1038/nature08197

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Hirschey MD, Shimazu T, Jing E, Grueter CA, Collins AM, Aouizerat B, Stancakova A, Goetzman E, Lam MM, Schwer B, Stevens RD, Muehlbauer MJ, Kakar S, Bass NM, Kuusisto J, Laakso M, Alt FW, Newgard CB, Farese RJ, Kahn CR, Verdin E (2011) SIRT3 deficiency and mitochondrial protein hyperacetylation accelerate the development of the metabolic syndrome. Mol Cell 44(2):177–190. doi:10.1016/j.molcel.2011.07.019

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Matovic V, Buha A, Ethukic-Cosic D, Bulat Z (2015) Insight into the oxidative stress induced by lead and/or cadmium in blood, liver and kidneys. Food Chem Toxicol 78:130–140. doi:10.1016/j.fct.2015.02.011

    Article  CAS  PubMed  Google Scholar 

  25. Marchlewicz M, Baranowska-Bosiacka I, Kolasa A, Kondarewicz A, Chlubek D, Wiszniewska B (2009) Disturbances of energetic metabolism in rat epididymal epithelial cells as a consequence of chronic lead intoxication. Biometals 22(6):877–887. doi:10.1007/s10534-009-9238-z

    Article  CAS  PubMed  Google Scholar 

  26. Marmolino D, Manto M, Acquaviva F, Vergara P, Ravella A, Monticelli A, Pandolfo M (2010) PGC-1alpha down-regulation affects the antioxidant response in Friedreich’s ataxia. PLoS One 5(4):e10025. doi:10.1371/journal.pone.0010025

    Article  PubMed  PubMed Central  Google Scholar 

  27. Sundaresan NR, Gupta M, Kim G, Rajamohan SB, Isbatan A, Gupta MP (2009) Sirt3 blocks the cardiac hypertrophic response by augmenting Foxo3a-dependent antioxidant defense mechanisms in mice. J Clin Invest 119(9):2758–2771. doi:10.1172/JCI39162

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Blanco G, Mercer RW (1998) Isozymes of the Na-K-ATPase: heterogeneity in structure, diversity in function. Am J Phys 275(5 Pt 2):F633–F650

    CAS  Google Scholar 

  29. Zeino M, Brenk R, Gruber L, Zehl M, Urban E, Kopp B, Efferth T (2015) Cytotoxicity of cardiotonic steroids in sensitive and multidrug-resistant leukemia cells and the link with Na(+)/K(+)-ATPase. J Steroid Biochem Mol Biol 150:97–111. doi:10.1016/j.jsbmb.2015.03.008

    Article  CAS  PubMed  Google Scholar 

  30. Mazzitelli LR, Rinaldi DE, Corradi GR, Adamo HP (2010) The plasma membrane Ca2+ pump catalyzes the hydrolysis of ATP at low rate in the absence of Ca2+. Arch Biochem Biophys 495(1):62–66. doi:10.1016/j.abb.2009.12.021

    Article  CAS  PubMed  Google Scholar 

  31. Bhatti JS, Sidhu IP, Bhatti GK (2011) Ameliorative action of melatonin on oxidative damage induced by atrazine toxicity in rat erythrocytes. Mol Cell Biochem 353(1–2):139–149. doi:10.1007/s11010-011-0780-y

    Article  CAS  PubMed  Google Scholar 

  32. Quintanar-Escorza MA, Gonzalez-Martinez MT, Del PI, Calderon-Salinas JV (2010) Oxidative damage increases intracellular free calcium [Ca2+]i concentration in human erythrocytes incubated with lead. Toxicol in Vitro 24(5):1338–1346. doi:10.1016/j.tiv.2010.05.002

    Article  CAS  PubMed  Google Scholar 

  33. Gokulakrishnan A, Ali AR (2010) Cigarette smoke-induced biochemical perturbations in human erythrocytes and attenuation by epigallocatechin-3-gallate—tea catechin. Pharmacol Rep 62(5):891–899

    Article  CAS  PubMed  Google Scholar 

  34. Nava-Ruiz C, Mendez-Armenta M, Rios C (2012) Lead neurotoxicity: effects on brain nitric oxide synthase. J Mol Histol 43(5):553–563. doi:10.1007/s10735-012-9414-2

    Article  CAS  PubMed  Google Scholar 

  35. Baranowska-Bosiacka I, Dziedziejko V, Safranow K, Gutowska I, Marchlewicz M, Dolegowska B, Rac ME, Wiszniewska B, Chlubek D (2009) Inhibition of erythrocyte phosphoribosyltransferases (APRT and HPRT) by Pb2+: a potential mechanism of lead toxicity. Toxicology 259(1–2):77–83. doi:10.1016/j.tox.2009.02.005

    Article  CAS  PubMed  Google Scholar 

  36. Robinson R, Fritz IB (1981) Metabolism of glucose by Sertoli cells in culture. Biol Reprod 24(5):1032–1041

    Article  CAS  PubMed  Google Scholar 

  37. Grootegoed JA, Oonk RB, Jansen R, van der Molen HJ (1986) Metabolism of radiolabelled energy-yielding substrates by rat Sertoli cells. J Reprod Fertil 77(1):109–118

    Article  CAS  PubMed  Google Scholar 

  38. Boussouar F, Benahmed M (2004) Lactate and energy metabolism in male germ cells. Trends Endocrinol Metab 15(7):345–350. doi:10.1016/j.tem.2004.07.003

    Article  CAS  PubMed  Google Scholar 

  39. Jutte NH, Grootegoed JA, Rommerts FF, van der Molen HJ (1981) Exogenous lactate is essential for metabolic activities in isolated rat spermatocytes and spermatids. J Reprod Fertil 62(2):399–405

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The authors thank all members in Professor CH. Wang’s laboratory in Wuhan University for their valuable assistance and Xiaojie Lu in Tongji University for the revision of the manuscript. The project was supported by The National Natural Science Foundation of China (No.81172628) and Open Fund of Hubei Provincial Key Laboratory for Applied Toxicology.

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Correspondence to Chunhong Wang or Siyuan Xu.

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The authors declare that there are no conflicts of interest.

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Xi Liu and Jingping Ye contributed equally to this study and share first authorship.

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Liu, X., Ye, J., Wang, L. et al. Protective Effects of PGC-1α Against Lead-Induced Oxidative Stress and Energy Metabolism Dysfunction in Testis Sertoli Cells. Biol Trace Elem Res 175, 440–448 (2017). https://doi.org/10.1007/s12011-016-0799-8

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