Abstract
In addition to playing a fundamental role in diverse processes, such as vision, growth and differentiation, vitamin A and its main biologically active derivative, retinoic acid (RA), are clearly involved in the regulation of testicular functions. The present study was undertaken to examine the direct effect of RA treatment on Leydig (TM-3) cells. TM-3 cells were cultured and treated with varying concentrations of RA for 24h. High doses of RA (1–20μM) induced a decrease in cell vitality and an increase in lipid peroxidation. RA treatment also induced a corresponding increase in apoptosis in the same cells in a dose-dependent manner. Apoptosis proceeded via the mitochondrial dependent pathway, as demonstrated by the release of cytochrome c, caspase-3 enzymatic activation and DNA fragmentation. Conversely, at physiological doses (0.1–500nM) RA did not increase lipid peroxidation or cell death and resulted in an increase of antioxidant enzyme activity.
Similar content being viewed by others
References
Abe K, Matsuki N (2000) Neurosci Res 38:325–329
Aebi H (1974) Catalase. In: Bergmeyer HU (ed) Methods in enzymatic analysis. Academic Press, New York, pp 631–684
Agarwal N, Mehta K (1997) Biochem Biophys Res Commun 230:251–253
Alam SQ, Alam BS, Chen TW (1984) Biochim Biophys Acta 792:110–117
Bose R, Verheij M, Haimovitz-Friedman A, Scotto K, Fuks Z, Kolesnick R (1995) Cell 82:405–414
Cai J, Yang J, Jones DP (1998) Biochim Biophys Acta 1366:139–149
Chambon P (1996) FASEB J 10:940–954
Cohen GM (1997) Biochem J 326:1–16
Das K, Samanta L, Chainy GBN (2000) IJBB 37:201–204
Davis WL, Crawford LA, Cooper OJ, Farmer GR, Thomas D, Freeman BL (1990) J Craniofac Genet Dev Biol 10:295–310
De Leen Heer AP, Lambert WE, Claeys I (1982) J Lipid Res 23:1362–1367
Delia D, Aiello A, Soligo D, Fontanella E, Melani C, Pezzella F, Pienotti MA, Della-Porta G (1992) Blood 79:1291–1298
Esterbauer H, Cheeseman KH (1990) Methods Enzymol 186:407–421
Garcia-Calvo M, Peterson EP, Rasper DM, Vaillancourt JP, Zamboni R, Nicholson DW, Thoberry NA (1999) Cell Death Differ 6:362–369
Giguere V (1994) Endocr Rev 15:61–79
Gudas LJ, Sporn MB, Roberts AB (1994) Cellular biology and biochemistry of the retinoids. In: Sporn MB, Roberts AB, Goodman DS (eds) The retinoids: biology, chemistry, and medicine. Raven Press, New York, pp 443–520
Habig WH, Pabst MJ, Jakoby WB (1973) J Biol Chem 249:7130–7139
Herbert V (1996) J Nutr 126:1197–1200
Horn R, Minucci C, Ogryzko VV, Adamson ED, Howard BH, Levin AA, Ozato K (1996) FASEB J 10:1071–1077
Hurnanen D, Chan M, Kubow S (1997) J Pharmacol Exp Ther 283:1520–1528
Kane MA, Chen N, Sparks S, Napoli JL (2005) Biochem J 388:363–369
Kerr JF, Wyllie AH, Currie AR (1997) Br J Cancer 26:239–257
Kim DG, Jo BH, You KR, Ahn DS (1996) Cancer Lett 107:149–159
Kolesnick R (2002) J Clin Invest 110:3–8
Li P, Nijhawan D, Budihardjo I, Srinivasula SM, Ahmad M, Alnemri ES, Wang X (1997) Cell 91:479–489
Li Y, Hashimoto Y, Agadir A, Kagechika H, Zhang X (1999) J Biol Chem 274:15360–15366
Liu X, Kim CN, Yang J, Jemmerson R, Wang X (1996) Cell 86:147–157
Livera G, Rouiller-Fabre V, Durand P, Habert R (2000) Biol Reprod 62:1303–1314
Livrea MA, Packer L (1993) Retinoids—progress in research and clinical applications. Dekker, New York
Lotan R (1996) FASEB J 10:1031–1039
Lowry OH, Rosebrough NJ, Randall RJ (1951) J Biol Chem 193:265–275
Lu XP, Fanjul A, Picard N, Pfahl M, Rungta D, Nared-Hood K, Carter B, Piedrafita J, Tang S, Fabbrizio E, Pfahl M (1997) Nat Med 3:686–690
Mosmann T (1983) J Immunol Methods 65:55–63
Mu YM, Yanase T, Nish Y, Tanaka A, Saito M, Jin C, Mukasa C, Okabe T, Nomura M, Goto K, Navata H (2001) Endocrinology 142:3590–3597
Nagata S (1997) Cell 88:355–365
Nagy LV, Thomazy GL, Shipley L, Fesus W, Lamph RA, Heyman RA, Chandraratna PJ (1995) Mol Cell Biol 15:3540–3551
Nakai M, Takeda A, Cleary ML, Endo T (1993) Biochem Biophys Res Commun 196:233–239
Nakamura N, Shidoji Y, Yamada Y, Hatakeyama H, Moriwaki H, Muto Y (1995) Biochem Biophys Res Commun 207:382–388
Pinton P, Ferrari D, Rapizzi E, Virgilio FD, Pozzan T, Rizzuto R (2001) EMBO J 20:2690–2701
Radominska-Pandya A, Chen G, Czernik PJ, Little JM, Samokyszyn VM, Carter CA, Nowak G (2000) J Biol Chem 275:22324–22330
Toma S, Isnardi L, Raffo P, Dastoli G, De Francisci E, Riccardi L, Palombo R, Bollag W (1997) Int J Cancer 70:619–627
Von Haefen C, Wieder T, Gillissen B, Starck L, Graupner V, Dorken B, Daniel PT (2002) Oncogene 21:4009–4019
Woodle ES, Kulkarni S (1998) Transplantation 66:681–691
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Tucci, P., Cione, E., Perri, M. et al. All-trans-retinoic acid induces apoptosis in Leydig cells via activation of the mitochondrial death pathway and antioxidant enzyme regulation. J Bioenerg Biomembr 40, 315–323 (2008). https://doi.org/10.1007/s10863-008-9156-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10863-008-9156-8