Abstract
Endoplasmic reticulum (ER) is an important organelle with functions like protein synthesis, folding, and calcium homeostasis. ER stress, a condition that dramatically affects protein folding homeostasis in cells, has been associated with a number of metabolic disorders. Emerging clinical and preclinical evidence support the notion that pharmacological modulators of ER stress have therapeutic potential as a novel target for treating metabolic diseases. ER is in physical contact with mitochondria, and there is a strong cross talk between these organelles at functional level. The present investigation was aimed to check the mitochondrial alterations in adipocytes with tunicamycin-induced ER stress and modulation by apigenin and quercetin. For this, differentiated adipocytes were incubated with tunicamycin (2 μg/ml) for 18 h, and changes in mitochondrial membrane potential, biogenesis, reactive oxygen species production, and adiponectin secretion were seen. Tunicamycin-induced ER stress altered reactive oxygen species (ROS) (6.34-fold↑), membrane potential (4.1-fold↑), mitochondrial biogenesis (2.4-fold↓), and adiponectin secretion (3.5-fold↓). Apigenin and quercetin ameliorated alterations in mitochondria. From results, we conclude that ER stress significantly alters mitochondrial functions and both the bioactives significantly protected mitochondrial alterations during ER stressand reestablished adiponectin secretion.
Similar content being viewed by others
References
Trayhurn, P., & Beattie, J. H. (2001). Proceedings of the Nutrition Society, 60, 329–339.
Boden, G., Duan, X., Homko, C., Molina, E. J., Song, W., Perez, O., Cheung, P., & Merali, S. (2008). Diabetes, 57, 2438–2444.
Kawasaki, N., Asada, R., Saito, A., Kanemoto, S., & Imaizumi, K. (2012). Scientific Reports, 2, 799.
Xu, C., Bailly-Maitre, B., & Reed, J. C. (2005). Journal of Clinical Investigation, 115(10), 2656–2664.
Gething, M. J., & Sambrook, J. (1992). Nature, 355, 33–45.
Tsuriya, D., Morita, H., Morioka, T., Takahashi, N., Ito, T., Oki, Y., & Nakamura, H. (2011). Internal Medicine, 50, 2767–2773.
Ellgaard, L., Molinari, M., & Helenius, A. (1999). Science, 286, 1882–1888.
Kaufman, R. J., Scheuner, D., Schroder, M., Shen, X., Lee, K., Liu, C. Y., & Arnold, S. M. (2002). Nature Reviews Molecular Cell Biology, 3, 411–421.
Ron, D. (2002). Journal of Clinical Investigation, 1110, 1383–1388.
Hayashi, T., Rizzuto, R., Hajnoczky, G., & Su, T. P. (2009). Trends in Cell Biology, 2, 81–88.
Simmen, T., Lynes, E. M., Gesson, K., & Thomas, G. (2010). Biochimica et Biophysica Acta, 1798, 1465–1473.
Mondal, A. K., Das, S. K., Varma, V., Nolen, G. T., McGehee, R. E., Elbein, S. C., Wei, J. Y., & Ranganathan, G. (2012). Metabolic Syndrome and Related Disorders, 10, 297–306.
Ozcan, L., Ayse Seda, E., Lu, A., Chung, J., Sarkar, S., Duyu, N., & Myers, M. G. (2009). Cell Metabolism, 9, 35–51.
Yun, J. W. (2010). Possible anti-obesity therapeutics from nature—a review. Phytochemistry, 71, 1625–1641.
Escande, C., Nin, V., Price, N. L., Capellini, V., Gomes, A. P., Barbosa, M. T., O'Neil, L., White, T. A., Sinclair, D. A., & Chini, E. N. (2013). Diabetes, 62(4), 1084–1093.
Lee, J. H., Zhou, H. Y., Cho, S. Y., Kim, Y. S., Lee, Y. S., & Jeong, C. S. (2007). Archives of Pharmacal Research, 30(10), 1318–27.
Stewart, L. K., Soileau, J. L., Ribnicky, D., Wang, Z. Q., Raskin, I., Poulev, A., Majewski, M., Cefalu, W. T., & Gettys, T. W. (2008). Metabolism, Clinical and Experimental, 57(7), S39–S46.
Berridge, M. J., Bootman, M. D., & Roderick, H. L. (2003). Nature Reviews Molecular, 4, 517–29.
Deniaud, A., Sharaf el dein, O., Maillier, E., Poncet, D., Kroemer, G., Lemaire, & Brenner, C. (2008). Oncogene, 27, 285–299.
Frizzell, N., Rajesh, M., Jepson, M. J., Nagai, R., Carson, J. A., Thorpe, S. R., & Baynes, J. W. (2009). Journal of Biological Chemistry, 284(38), 25772–81.
Cao, S. S., & Randal, J. K. (2013). Expert Opinion on Therapeutic Targets, 17, 437–448.
Nabin, R., Kim, S. K., Go, H., Joe, Y., Callaway, Z., Kang, J. G., Ryter, S. W., & Chung, H. T. (2013). Oxidative Medicine and Cellular Longevity. doi:10.1155/2013/154279.
Estruch, R., Ros, E., Salas-Salvado, J., Covas, M. I., Corella, D., Aros, F., Gomez-Gracia, E., Ruiz-Gutierrez, V., Fiol, M., & Lapetra, J. (2013). New England Journal of Medicine, 368, 1279–1290.
Nicholas, C., Batra, S., Vargo, M. A., Voss, O. H., Gavrilin, M. A., Wewers, M. D., Guttridge, D. C., Grotewold, E., & Doseff, A. (2007). Journal of Immunology, 179, 7121–7127.
Acknowledgments
We thank Council for Scientific and Industrial Research, Govt. of India, for financial assistance in the form of research fellowship. We are also thankful to the CSIR 12th 5-year plan project “NaPAHA” for financial support. We thank the Director, CSIR-NIIST, and Head, Agroprocessing and Natural Products Division, for providing necessary facilities.
Conflict of Interest
There is no conflict of interest existing between the authors.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Nisha, V.M., Anusree, S.S., Priyanka, A. et al. Apigenin and Quercetin Ameliorate Mitochondrial Alterations by Tunicamycin-Induced ER Stress in 3T3-L1 Adipocytes. Appl Biochem Biotechnol 174, 1365–1375 (2014). https://doi.org/10.1007/s12010-014-1129-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12010-014-1129-2