Swainsonine induces apoptosis of rat cardiomyocytes via mitochondria"‘mediated pathway

Xiang Zheng; Shushu Wang; Dakai Chen; Xiaoming Yang

doi:10.14715/cmb/2018.64.5.23

Issue

Vol. 64 No. 5: Issue 5

Issue Published : May 1, 2018

The undersigned hereby assign all rights, included but not limited to copyright, for this manuscript to CMB Association upon its submission for consideration to publication on Cellular and Molecular Biology. The rights assigned include, but are not limited to, the sole and exclusive rights to license, sell, subsequently assign, derive, distribute, display and reproduce this manuscript, in whole or in part, in any format, electronic or otherwise, including those in existence at the time this agreement was signed. The authors hereby warrant that they have not granted or assigned, and shall not grant or assign, the aforementioned rights to any other person, firm, organization, or other entity. All rights are automatically restored to authors if this manuscript is not accepted for publication.

Swainsonine induces apoptosis of rat cardiomyocytes via mitochondria"‘mediated pathway

https://doi.org/10.14715/cmb/2018.64.5.23

Xiang Zheng

Department of Cardiology, Wenzhou Hospital of Integrated Traditional Chinese and Western medicine, NO.75,Jinxiu Road, Wenzhou, Zhejiang 325027, China

Shushu Wang

Department of Cardiology, Wenzhou Hospital of Integrated Traditional Chinese and Western medicine, NO.75,Jinxiu Road, Wenzhou, Zhejiang 325027, China

Dakai Chen

Department of Cardiology, Wenzhou Hospital of Integrated Traditional Chinese and Western medicine, NO.75,Jinxiu Road, Wenzhou, Zhejiang 325027, China

Xiaoming Yang

Department of Cardiology, Wenzhou Hospital of Integrated Traditional Chinese and Western medicine, NO.75,Jinxiu Road, Wenzhou, Zhejiang 325027, China

Corresponding Author(s) : Xiaoming Yang

xp1344@163.com

Cellular and Molecular Biology, Vol. 64 No. 5: Issue 5
Article Published : April 30, 2018

Abstract

Swainsonine is an Astragalus membranaceus extract. It is indole, alkaloid, and soluble in water. Its effect on rat cardiomyocytes apoptosis, and the mechanisms underlying that effect, were investigated by inducing apoptosis in H9c2 cells. This was detected by MTT assay, Annexin V-FITC/propidium iodide double staining and western blotting. Flow cytometry and fluorescence microscopy were used to confirm swainsonine's effect on mitochondrial membrane potential and levels of reactive oxygen species, while an ATP-dependent bioluminescence assay kit served to find the ATP contents. Assessment was also carried out for peroxisome proliferator activated receptor Î³ co-activator 1Î± (PGC-1Î±) expression levels as well as those of such apoptosis-associated proteins as Cytochrome c, Caspase-3, B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax). Overall, indications were that swainsonine may have the potential to inhibit viability of cells, decrease expression of PGC-1Î±, induce mitochondrial dysfunction, upregulate Cytochrome c, Bax and Caspase-3, and downregulate Bcl-2. The suggestion would be that apoptosis may be induced through signalling pathways in H9c2 cells mediated by mitochondria.

Keywords

Swainsonine Apoptosis Rat cardiomyocytes Mitochondria"‘mediated pathway.

Zheng, X., Wang, S., Chen, D., & Yang, X. (2018). Swainsonine induces apoptosis of rat cardiomyocytes via mitochondria"‘mediated pathway. Cellular and Molecular Biology, 64(5), 136–141. https://doi.org/10.14715/cmb/2018.64.5.23

Download Citation

References

Lu H, Wang S S, Wang W L, Zhang L, Zhao B Y. Effect of swainsonine in Oxytropis kansuensis on Golgi Î±-mannosidase II expression in the brain tissues of Sprague-Dawley rats.
Journal of Agricultural & Food Chemistry 2014; 62: 7407.
Cook D, Gardner D R, Lee S T, Pfister J A, Stonecipher C A, Welsh S L. A swainsonine survey of North American Astragalus and Oxytropis taxa implicated as locoweeds. Toxicon 2016; 118: 104-11.
Lu H, Ma F, Wang H, Geng P S, Wang S S, Wang J G, et al. The effects of swainsonine on the activity and expression of íŽ±-mannosidase in BRL-3A cells. Toxicon 2015; 99: 44-50.
Wu C, Liu X, Feng M, Zhao B. Hematological and histopathological effects of swainsonine in mouse. Bmc Veterinary Research 2015; 11: 1-8.
Sun J Y, Zhu M Z, Wang S W, Miao S, Xie Y H, Wang J B. Inhibition of the growth of human gastric carcinoma in vivo and in vitro by swainsonine. Phytomedicine 2007; 14: 353-59.
Kakkar P, Singh B K. Mitochondria: a hub of redox activities and cellular distress control. Molecular & Cellular Biochemistry 2007; 305: 235-53.
Won J C, Park J Y, Kim Y M, Koh E H, Seol S, Jeon B H, et al. Peroxisome proliferator-activated receptor-gamma coactivator 1-alpha overexpression prevents endothelial apoptosis by increasing ATP/ADP translocase activity. Arterioscler Thromb Vasc Biol 2010; 30: 290-97.
Patten I S, Arany Z. PGC-1 coactivators in the cardiovascular system. Trends in Endocrinology & Metabolism Tem 2012; 23: 90-97.
Ding F, Shao Z W, Yang S H, Wu Q, Gao F, Xiong L M. Role of mitochondrial pathway in compression-induced apoptosis of nucleus pulposus cells. Apoptosis 2012; 17: 579-90.
Babbitt S E, Sutherland M C, Francisco B S, Mendez D L, Kranz R G. Mitochondrial cytochrome c biogenesis: no longer an enigma. Trends in Biochemical Sciences 2015; 40: 446-55.
Wei H, Li Z, Hu S, Chen X, Cong X. Apoptosis of mesenchymal stem cells induced by hydrogen peroxide concerns both endoplasmic reticulum stress and mitochondrial death pathway through regulation of caspases, p38 and JNK. Journal of Cellular Biochemistry 2010; 111: 967-78.
Sun J Y, Yang H, Miao S, Li J P, Wang S W, Zhu M Z, et al. Suppressive effects of swainsonine on C6 glioma cell in vitro and in vivo. Phytomedicine 2009; 16: 1070-74.
Hu Y, Wu L, Wang C, Luo J, Liao F, Tan H, et al. Swainsonine exposure induces impairment of host immune response in pregnant BALB/c mice. Bmc Immunology 2015; 16: 53.
Hao L, Feng M, Liang Z, Wang J, Wu C, Zhao B. Swainsonine-induced apoptosis pathway in cerebral cortical neurons. Research in Veterinary Science 2015; 102: 34-37.
Panter K E, James L F, Stegelmeier B L, Ralphs M H, Pfister J A. Locoweeds: effects on reproduction in livestock. Journal of Natural Toxins 1999; 8: 53.
Riba A, Deres L, Eros K, Szabo A, Magyar K, Sumegi B, et al. Doxycycline protects against ROS-induced mitochondrial fragmentation and ISO-induced heart failure. Plos One 2017; 12: e0175195.
Schilling J. The Mitochondria in Diabetic Heart Failure: from pathogenesis to therapeutic promise. Antioxidants & Redox Signaling 2015; 22: 1515.
Miyamoto S, Murphy A N, Brown J H. Akt mediates mitochondrial protection in cardiomyocytes through phosphorylation of mitochondrial hexokinase-II. Cell Death & Differentiation 2008; 15: 521-29.
Ly J D, Grubb D R, Lawen A. The mitochondrial membrane potential (Î”Ïˆm) in apoptosis; an update. Apoptosis An International Journal on Programmed Cell Death 2003; 8: 115-28.
Fang H, Chen M, Ding Y, Shang W, Xu J, Zhang X, et al. Imaging superoxide flash and metabolism-coupled mitochondrial permeability transition in living animals. Cell Research 2011; 21: 1295-304.
Russell L K, Mansfield C M, Lehman J J, Kovacs A, Courtois M, Saffitz J E, et al. Cardiac-Specific Induction of the Transcriptional Coactivator Peroxisome Proliferator-Activated Receptor Î³ Coactivator-1Î± Promotes Mitochondrial Biogenesis and Reversible Cardiomyopathy in a Developmental Stage-Dependent Manner. Circulation Research 2004; 94: 525-33.
Luo G, Xu X, Wei G, Luo C, Hao W, Meng X, et al. Neuropeptide Y damages the integrity of mitochondrial structure and disrupts energy metabolism in cultured neonatal rat cardiomyocytes. Peptides 2015; 71: 162-69.
Olson M, Kornbluth S. Mitochondria in apoptosis and human disease. Current Molecular Medicine 2001; 1: -.
Hardwick J M, Chen Y, Jonas E A. Multipolar functions of BCL-2 proteins link energetics to apoptosis. Trends in Cell Biology 2012; 22: 318-28.
Rao S R, Sundararajan S, Subbarayan R, Murugan G D. Cyclosporine-A induces endoplasmic reticulum stress and influences pro-apoptotic factors in human gingival fibroblasts. Molecular & Cellular Biochemistry 2017; 429: 179-85.
Ravindran J, Gupta N, Agrawal M, Bala Bhaskar A S, Lakshmana Rao P V. Modulation of ROS/MAPK signaling pathways by okadaic acid leads to cell death via, mitochondrial mediated caspase-dependent mechanism. Apoptosis 2011; 16: 145.
Feilchenfeldt J, Bründler M A, Soravia C, Tötsch M, Meier C A. Peroxisome proliferator-activated receptors (PPARs) and associated transcription factors in colon cancer: reduced expression of PPARgamma-coactivator 1 (PGC-1). Cancer Letters 2004; 203: 25-33.
Zhang Y, Ba Y, Liu C, Sun G, Ding L, Gao S, et al. PGC-1|[alpha]| induces apoptosis in human epithelial ovarian cancer cells through a PPAR|[gamma]|-dependent pathway. Cell Research 2007; 17: 363.
Yang Y, Zhang H, Li X, Yang T, Jiang Q. Effects of PPARÎ±/PGC-1Î± on the energy metabolism remodeling and apoptosis in the doxorubicin induced mice cardiomyocytes in vitro. International Journal of Clinical & Experimental Pathology 2015; 8: 12216.

References

Lu H, Wang S S, Wang W L, Zhang L, Zhao B Y. Effect of swainsonine in Oxytropis kansuensis on Golgi Î±-mannosidase II expression in the brain tissues of Sprague-Dawley rats.

Journal of Agricultural & Food Chemistry 2014; 62: 7407.

Cook D, Gardner D R, Lee S T, Pfister J A, Stonecipher C A, Welsh S L. A swainsonine survey of North American Astragalus and Oxytropis taxa implicated as locoweeds. Toxicon 2016; 118: 104-11.

Lu H, Ma F, Wang H, Geng P S, Wang S S, Wang J G, et al. The effects of swainsonine on the activity and expression of íŽ±-mannosidase in BRL-3A cells. Toxicon 2015; 99: 44-50.

Wu C, Liu X, Feng M, Zhao B. Hematological and histopathological effects of swainsonine in mouse. Bmc Veterinary Research 2015; 11: 1-8.

Sun J Y, Zhu M Z, Wang S W, Miao S, Xie Y H, Wang J B. Inhibition of the growth of human gastric carcinoma in vivo and in vitro by swainsonine. Phytomedicine 2007; 14: 353-59.

Kakkar P, Singh B K. Mitochondria: a hub of redox activities and cellular distress control. Molecular & Cellular Biochemistry 2007; 305: 235-53.

Won J C, Park J Y, Kim Y M, Koh E H, Seol S, Jeon B H, et al. Peroxisome proliferator-activated receptor-gamma coactivator 1-alpha overexpression prevents endothelial apoptosis by increasing ATP/ADP translocase activity. Arterioscler Thromb Vasc Biol 2010; 30: 290-97.

Patten I S, Arany Z. PGC-1 coactivators in the cardiovascular system. Trends in Endocrinology & Metabolism Tem 2012; 23: 90-97.

Ding F, Shao Z W, Yang S H, Wu Q, Gao F, Xiong L M. Role of mitochondrial pathway in compression-induced apoptosis of nucleus pulposus cells. Apoptosis 2012; 17: 579-90.

Babbitt S E, Sutherland M C, Francisco B S, Mendez D L, Kranz R G. Mitochondrial cytochrome c biogenesis: no longer an enigma. Trends in Biochemical Sciences 2015; 40: 446-55.

Wei H, Li Z, Hu S, Chen X, Cong X. Apoptosis of mesenchymal stem cells induced by hydrogen peroxide concerns both endoplasmic reticulum stress and mitochondrial death pathway through regulation of caspases, p38 and JNK. Journal of Cellular Biochemistry 2010; 111: 967-78.

Sun J Y, Yang H, Miao S, Li J P, Wang S W, Zhu M Z, et al. Suppressive effects of swainsonine on C6 glioma cell in vitro and in vivo. Phytomedicine 2009; 16: 1070-74.

Hu Y, Wu L, Wang C, Luo J, Liao F, Tan H, et al. Swainsonine exposure induces impairment of host immune response in pregnant BALB/c mice. Bmc Immunology 2015; 16: 53.

Hao L, Feng M, Liang Z, Wang J, Wu C, Zhao B. Swainsonine-induced apoptosis pathway in cerebral cortical neurons. Research in Veterinary Science 2015; 102: 34-37.

Panter K E, James L F, Stegelmeier B L, Ralphs M H, Pfister J A. Locoweeds: effects on reproduction in livestock. Journal of Natural Toxins 1999; 8: 53.

Riba A, Deres L, Eros K, Szabo A, Magyar K, Sumegi B, et al. Doxycycline protects against ROS-induced mitochondrial fragmentation and ISO-induced heart failure. Plos One 2017; 12: e0175195.

Schilling J. The Mitochondria in Diabetic Heart Failure: from pathogenesis to therapeutic promise. Antioxidants & Redox Signaling 2015; 22: 1515.

Miyamoto S, Murphy A N, Brown J H. Akt mediates mitochondrial protection in cardiomyocytes through phosphorylation of mitochondrial hexokinase-II. Cell Death & Differentiation 2008; 15: 521-29.

Ly J D, Grubb D R, Lawen A. The mitochondrial membrane potential (Î”Ïˆm) in apoptosis; an update. Apoptosis An International Journal on Programmed Cell Death 2003; 8: 115-28.

Fang H, Chen M, Ding Y, Shang W, Xu J, Zhang X, et al. Imaging superoxide flash and metabolism-coupled mitochondrial permeability transition in living animals. Cell Research 2011; 21: 1295-304.

Russell L K, Mansfield C M, Lehman J J, Kovacs A, Courtois M, Saffitz J E, et al. Cardiac-Specific Induction of the Transcriptional Coactivator Peroxisome Proliferator-Activated Receptor Î³ Coactivator-1Î± Promotes Mitochondrial Biogenesis and Reversible Cardiomyopathy in a Developmental Stage-Dependent Manner. Circulation Research 2004; 94: 525-33.

Luo G, Xu X, Wei G, Luo C, Hao W, Meng X, et al. Neuropeptide Y damages the integrity of mitochondrial structure and disrupts energy metabolism in cultured neonatal rat cardiomyocytes. Peptides 2015; 71: 162-69.

Olson M, Kornbluth S. Mitochondria in apoptosis and human disease. Current Molecular Medicine 2001; 1: -.

Hardwick J M, Chen Y, Jonas E A. Multipolar functions of BCL-2 proteins link energetics to apoptosis. Trends in Cell Biology 2012; 22: 318-28.

Rao S R, Sundararajan S, Subbarayan R, Murugan G D. Cyclosporine-A induces endoplasmic reticulum stress and influences pro-apoptotic factors in human gingival fibroblasts. Molecular & Cellular Biochemistry 2017; 429: 179-85.

Ravindran J, Gupta N, Agrawal M, Bala Bhaskar A S, Lakshmana Rao P V. Modulation of ROS/MAPK signaling pathways by okadaic acid leads to cell death via, mitochondrial mediated caspase-dependent mechanism. Apoptosis 2011; 16: 145.

Feilchenfeldt J, Bründler M A, Soravia C, Tötsch M, Meier C A. Peroxisome proliferator-activated receptors (PPARs) and associated transcription factors in colon cancer: reduced expression of PPARgamma-coactivator 1 (PGC-1). Cancer Letters 2004; 203: 25-33.

Zhang Y, Ba Y, Liu C, Sun G, Ding L, Gao S, et al. PGC-1|[alpha]| induces apoptosis in human epithelial ovarian cancer cells through a PPAR|[gamma]|-dependent pathway. Cell Research 2007; 17: 363.

Yang Y, Zhang H, Li X, Yang T, Jiang Q. Effects of PPARÎ±/PGC-1Î± on the energy metabolism remodeling and apoptosis in the doxorubicin induced mice cardiomyocytes in vitro. International Journal of Clinical & Experimental Pathology 2015; 8: 12216.

Author biographies is not available.