nach oben

Cardiovascular Toxicology

Erschienen in:

15.05.2019

Acylated Ghrelin Protects the Hearts of Rats from Doxorubicin-Induced Fas/FasL Apoptosis by Stimulating SERCA2a Mediated by Activation of PKA and Akt

verfasst von: Ali A. Shati, M. Dallak

Erschienen in: Cardiovascular Toxicology | Ausgabe 6/2019

Einloggen, um Zugang zu erhalten

Abstract

This study investigated if the cardioprotective effect of acylated ghrelin (AG) against doxorubicin (DOX)-induced cardiac toxicity in rats involves inhibition of Fas/FasL-mediated cell death. It also investigated if such an effect is mediated by restoring Ca⁺² homeostasis from the aspect of stimulation of SERCA2a receptors. Adult male Wistar rats were divided into 4 groups (20 rats/each) as control, control + AG, DOX, and DOX + AG. AG was co-administered to all rats consecutively for 35 days. In addition, isolated cardiomyocytes were cultured and treated with AG in the presence or absence of DOX with or without pre-incubation with [d-Lys3]-GHRP-6 (a AG receptor antagonist), VIII (]an Akt inhibitor), or KT-5720 (a PKA inhibitor). AG increased LVSP, dp/dt_max, and dp/dt_min in both control and DOX-treated animals and improved cardiac ultrastructural changes in DOX-treated rats. It also inhibited ROS in control rats and lowered LVEDP, intracellular levels of ROS and Ca²⁺, and activity of calcineurin in LVs of DOX-treated rats. Concomitantly, it inhibited LV NFAT-4 nuclear translocation and downregulated their protein levels of Fas and FasL. Mechanistically, in control or DOX-treated hearts or cells, AG upregulated the levels of SERCA2a and increased the activities of PKA and Akt, leading to increase phosphorylation of phospholamban at Ser¹⁶ and Thr¹⁷. All these effects were abolished by d-Lys3-GHRP-6, VIII, or KT-5720 and were independent of food intake or GH/IGF-1. In conclusion, AG cardioprotection against DOX involves inhibition of extrinsic cell death and restoring normal Ca⁺² homeostasis.

Shi, J., Abdelwahid, E., & Wei, L. (2011). Apoptosis in anthracycline cardiomyopathy. Current Pediatric Reviews, 7, 329–336.PubMedPubMedCentral

Thorn, C. F., Oshiro, C., Marsh, S., Hernandez-Boussard, T., McLeod, H., Klein, T. E., et al. (2011). Doxorubicin pathways: Pharmacodynamics and adverse effects. Pharmacogenetics and Genomics, 21, 440–446.PubMedPubMedCentral

Wallace, K. B. (2007). Adriamycin-induced interference with cardiac mitochondrial calcium homeostasis. Cardiovascular Toxicology, 7, 101–107.PubMed

Niu, J., Azfer, A., Wang, K., Wang, X., & Kolattukudy, P. E. (2009). Cardiac-targeted expression of soluble Fas attenuates doxorubicin-induced cardiotoxicity in mice. Journal of Pharmacology and Experimental Therapeutics, 328, 740–748.PubMed

Kalivendi, S. V., Konorev, E. A., Cunningham, S., Vanamala, S. K., Kaji, E. H., Joseph, J., et al. (2005). Doxorubicin activates nuclear factor of activated T-lymphocytes and Fas ligand transcription: Role of mitochondrial reactive oxygen species and calcium. Biochemical Journal, 389, 527–539.PubMedPubMedCentral

Tsutamoto, T., Wada, A., Maeda, K., Mabuchi, N., Hayashi, M., Tsutsui, T., et al. (2001). Relationship between plasma levels of cardiac natriuretic peptides and soluble Fas: Plasma soluble Fas as a prognostic predictor in patients with congestive heart failure. J Card Fail., 7, 322–328.PubMed

Yamaguchi, S., Suzuki, T., Okuyama, M., Nitobe, J., Nakamura, N., Mitsui, Y., et al. (2000). Apoptosis in rat cardiac myocytes induced by Fas ligand: Priming for Fas-mediated apoptosis with doxorubicin. Journal of Molecular and Cellular Cardiology, 32, 881–889.PubMed

Wehrens, X. H., & Marks, A. R. (2004). Novel therapeutic approaches for heart failure by normalizing calcium cycling’. Nature Reviews Drug Discovery, 3, 565–573.PubMed

Schmidt, U., Hajjar, R. J., Helm, P. A., Kim, C. S., Doye, A. A., & Gwathmey, J. K. (1998). Contribution of abnormal sarcoplasmic reticulum ATPase activity to systolic and diastolic dysfunction in human heart failure. Journal of Molecular and Cellular Cardiology., 30, 1929–1937.PubMed

10.

Schmidt, U., Hajjar, R. J., Kim, C. S., Lebeche, D., Doye, A. A., & Gwathmey, J. K. (1999). Human heart failure: cAMP stimulation of SR Ca(2+)-ATPase activity and phosphorylation level of phospholamban. American Journal of Physiology, 277, H474–H480.PubMed

11.

Marks, A. R. (2013). Calcium cycling proteins and heart failure: Mechanisms and therapeutics. The Journal of Clinical Investigation, 123, 46–52.PubMedPubMedCentral

12.

Seth, M., Sumbilla, C., Mullen, S. P., Lewis, D., Klein, M. G., Hussain, A., et al. (2004). Sarco(endo)plasmic reticulum Ca²⁺ATPase (SERCA) gene silencing and remodeling of the Ca²⁺ signaling mechanism in cardiac myocytes. Proceedings of the National academy of Sciences of the United States of America, 101, 16683–16688.PubMedPubMedCentral

13.

Dodd, D. A., Atkinson, J. B., Olson, R. D., Buck, S., Cusack, B. J., Fleischer, S., et al. (1993). Doxorubicin cardiomyopathy is associated with a decrease in calcium release channel of the sarcoplasmic reticulum in a chronic rabbit model. J Clin Invest., 91, 1697–1705.PubMedPubMedCentral

14.

Arai, M., Tomaru, K., Takizawa, T., Sekiguchi, K., Yokoyama, T., Suzuki, T., et al. (1998). Sarcoplasmic reticulum genes are selectively down-regulated in cardiomyopathy produced by doxorubicin in rabbits. Journal of Molecular and Cellular Cardiology, 30, 243–254.PubMed

15.

Arai, M., Yoguchi, A., Takizawa, T., Yokoyama, T., Kanda, T., Kurabayashi, M., et al. (2000). Mechanism of doxorubicin-induced inhibition of sarcoplasmic reticulum Ca21-ATPase Gene transcription. Circulation Research, 86, 8–14.PubMed

16.

Tada, M. (2003). Calcium cycling proteins of the cardiac sarcoplasmic reticulum. Circulation Journal, 67, 729–737.PubMed

17.

Vangheluwe, P., Sipido, K. R., Raeymaekers, L., & Wuytack, F. (2006). New perspectives on the role of SERCA2′s Ca²⁺ affinity in cardiac function. Biochimica et Biophysica Acta, 1763, 1216–1228.PubMed

18.

Fearnley, C. J., Roderick, H. L., & Bootman, M. D. (2011). Calcium signaling in cardiac myocytes. Cold Spring Harbor Perspectives in Biology, 3, a004242.PubMedPubMedCentral

19.

Jo, S. H., Leblais, V., Wang, P. H., Crow, M. T., & Xiao, R. P. (2002). Phosphatidylinositol 3-kinase functionally compartmentalizes the concurrent G(s) signaling during beta2-adrenergic stimulation. Circulation Research, 91, 46–53.PubMed

20.

Gao, M. H., Tang, T., Guo, T., Miyanohara, A., Yajima, T., Pestonjamasp, K., et al. (2008). Adenylyl cyclase type VI increases Akt activity and phospholamban phosphorylation in cardiac myocytes. The Journal of Biological Chemistry., 283, 33527–33535.PubMedPubMedCentral

21.

Catalucci, D., Latronico, M. V., Ceci, M., Rusconi, F., Young, H. S., Gallo, P., et al. (2009). Akt increases sarcoplasmic reticulum Ca²⁺ cycling by direct phosphorylation of phospholamban at Thr17. The Journal of Biological Chemistry, 284, 28180–28187.PubMedPubMedCentral

22.

Zhang, Y., Chen, Y., Zhang, M., Tang, Y., Xie, Y., Huang, X., et al. (2014). Doxorubicin induces sarcoplasmic reticulum calcium regulation dysfunction via the decrease of SERCA2 and phospholamban expressions in rats. Cell Biochemistry and Biophysics, 70, 1791–1798.PubMed

23.

Zhang, G., Yin, X., Qi, Y., Pendyala, L., Chen, J., Hou, D., et al. (2010). Ghrelin and cardiovascular diseases. Current Cardiology Reviews, 6, 62–70.PubMedPubMedCentral

24.

Eid, R. A., Alkhateeb, M. A., Eleawa, S., Al-Hashem, F. H., Al-Shraim, M., El-Kott, A. F., et al. (2018). Cardioprotective effect of ghrelin against myocardial infarction-induced left ventricular injury via inhibition of SOCS3 and activation of JAK2/STAT3 signaling. Basic Research in Cardiology, 113, 13.PubMed

25.

Gnanapavan, S., Kola, B., Bustin, S. A., Morris, D. G., McGee, P., Fairclough, P., et al. (2002). The tissue distribution of the mRNA of ghrelin and subtypes of its receptor, GHS-R, in humans. Journal of Clinical Endocrinology and Metabolism, 87, 2988.PubMed

26.

Iglesias, M. J., Piñeiro, R., Blanco, M., Gallego, R., Diéguez, C., Gualillo, O., et al. (2004). Lago F growth hormone releasing peptide (ghrelin) is synthesized and secreted by cardiomyocytes. Cardiovascular Research, 62, 481–488.PubMed

27.

Baldanzi, G., Filigheddu, N., Cutrupi, S., Catapano, F., Bonissoni, S., Fubini, A., et al. (2002). Ghrelin and des-acyl ghrelin inhibit cell death in cardiomyocytes and endothelial cells through ERK1/2 and PI 3-kinase/AKT. Journal of Cell Biology, 159, 1029–1037.PubMedPubMedCentral

28.

Xu, Z., Lin, S., Wu, W., Tan, H., Wang, Z., Cheng, C., et al. (2008). Ghrelin prevents doxorubicin-induced cardiotoxicity through TNF-alpha/NF-kappaB pathways and mitochondrial protective mechanisms. Toxicology, 247, 133–138.PubMed

29.

Fang, H., Hong, Z., Zhang, J., Shen, D. F., Gao, F. F., Sugiyama, K., et al. (2012). Effects of ghrelin on the intracellular calcium concentration in rat aorta vascular smooth muscle cells. Cellular Physiology and Biochemistry., 30, 1299–1309.PubMed

30.

Han, D., Huang, W., Ma, S., Chen, J., Gao, L., Liu, T., et al. (2015). Ghrelin improves functional survival of engrafted adipose-derived mesenchymal stem cells in ischemic heart through PI3K/Akt signaling pathway. BioMed Research International. https://doi.org/10.1155/2015/858349.CrossRefPubMedPubMedCentral

31.

Lou, H., Danelisen, I., & Singal, P. K. (2005). Involvement of mitogen-activated protein kinases in adriamycininduced cardiomyopathy. The American Journal of Physiology-Heart and Circulatory Physiology, 288, 1925–1930.

32.

Dallak, M. (2018). Acylated ghrelin induces but deacylated ghrelin prevents hepatic steatosis and insulin resistance in lean rats: Effects on DAG/PKC/JNK pathway. Biomedicine & Pharmacotherapy, 105, 299–311.

33.

Li, Y., Hai, J., Li, L., Chen, X., Peng, H., Cao, M., et al. (2013). Administration of ghrelin improves inflammation, oxidative stress, and apoptosis during and after non-alcoholic fatty liver disease development. Endocrin., 43, 376–386.

34.

Işeri, S. O., Sener, G., Saglam, B., Ercan, F., Gedik, N., & Yeğen, B. C. (2008). Ghrelin alleviates biliary obstruction-induced chronic hepatic injury in rats. Regulatory Peptides, 146, 73–79.PubMed

35.

Donthi, R. V., Huisamen, B., & Lochner, A. (2000). Effect of vanadate and insulin on glucose transport in isolated adult rat cardiomyocytes. Cardiovascular Drugs and Therapy, 14, 463–470.PubMed

36.

Pentassuglia, L., Heim, P., Lebboukh, S., Morandi, C., Xu, L., & Brink, M. (2016). Neuregulin-1β promotes glucose uptake via PI3K/Akt in neonatal rat cardiomyocytes. American Journal of Physiology Endocrinology and Metabolism, 310, E782–E794.PubMed

37.

Dong, J., Gao, C., Liu, J., Cao, Y., & Tian, L. (2016). TSH inhibits SERCA2a and the PKA/PLN pathway in rat cardiomyocytes. Oncotarget, 7, 39207–39215.PubMedPubMedCentral

38.

Xu, J., Han, Q., Shi, H., Liu, W., Chu, T., & Li, H. (2017). Role of PKA in the process of neonatal cardiomyocyte hypertrophy induced by urotensin II. International Journal of Molecular Medicine, 40, 499–504.PubMed

39.

Frutos, M. G., Cacicedo, L., Méndez, C. F., Vicent, D., González, M., & Sánchez-Franco, F. (2007). Pituitary alterations involved in the decline of growth hormone gene expression in the pituitary of aging rats. Journals of Gerontology Series A Biological Sciences and Medical Sciences, 62, 585–597.PubMed

40.

Buehlmeyer, K., Doering, F., Daniel, H., Petridou, A., Mougios, V., Schulz, T., et al. (2007). IGF-1 gene expression in rat colonic mucosa after different exercise volumes. Journal of Sports Science and Medicine, 6, 434–440.PubMedPubMedCentral

41.

Zhao, X., Zhang, J., Tong, N., Chen, Y., & Luo, Y. (2012). Protective effects of berberine on doxorubicin-induced hepatotoxicity in mice. Biological &/and Pharmaceutical Bulletin, 35(5), 796–800.

42.

Mohan, M., Kamble, S., Gadhi, P., & Kasture, S. (2010). Protective effect of Solanum torvum on doxorubicin-induced nephrotoxicity in rats. Food and Chemical Toxicology, 4, 436–440.

43.

Jensen, R. A., Acton, E. M., & Peters, H. (1984). Doxorubicin cardiotoxicity in the rat: Comparison of electrocardiogram, transmembrane potential, and structural effect. Journal of Cardiovascular Pharmacology, 6, 186–200.PubMed

44.

Siveski-Iliskovic, N., Kaul, N., & Singal, P. K. (1994). Probucol promotes endogenous antioxidants and provides protection against adriamycin-induced cardiomyopathy in rats. Circulation, 89, 2829–2835.PubMed

45.

Childs, A. C., Phaneuf, S. L., Dirks, A. J., Phillips, T., & Leeuwenburgh, C. (2002). Doxorubicin treatment in vivo causes cytochrome C release and cardiomyocyte apoptosis, as well as increased mitochondrial efficiency, superoxide dismutase activity, and Bcl-2: Bax ratio. Cancer Research, 62, 4592–4598.PubMed

46.

Miyata, S., Takemura, G., Kosai, K., Takahashi, T., Esaki, M., Li, L., et al. (2010). Anti-Fas gene therapy prevents doxorubicin-induced acute cardiotoxicity through mechanisms independent of apoptosis. American Journal of Pathology, 176, 687–698.PubMedPubMedCentral

47.

Tian, S., Hirshfield, K. M., Jabbour, S., Toppmeyer, D., Haffty, B. G., Khan, A. J., et al. (2014). Serum biomarkers for the detection of cardiac toxicity after chemotherapy and radiation therapy in breast cancer patients. Frontiers in Oncology, 4, 277.PubMedPubMedCentral

48.

Chatterjee, K., Zhang, J., Honbo, N., & Karlinerb, J. S. (2010). Doxorubicin cardiomyopathy. Cardiology, 115, 155–162.PubMed

49.

Mitry, M. A., & Edwards, J. G. (2016). Doxorubicin induced heart failure: Phenotype and molecular mechanisms. International Journal of Cardiology Heart & Vasculature., 10, 17–24.

50.

Warpe, V. S., Mali, V. R., Arulmozhi, S., Bodhankar, S. L., & Mahadik, K. R. (2015). Cardioprotective effect of ellagic acid on doxorubicin induced cardiotoxicity in wistar rats. Journal of Acute Medicine, 5, 1–8.

51.

Nagaya, N., Uematsu, M., Kojima, M., Ikeda, Y., Yoshihara, F., Shimizu, W., et al. (2001). Chronic administration of ghrelin improves left ventricular dysfunction and attenuates development of cardiac cachexia in rats with heart failure. Circulation, 104, 1430–1435.PubMed

52.

Chen, Y., Ji, X. W., Zhang, A. Y., Lv, J. C., Zhang, J. G., & Zhao, C. H. (2014). Prognostic value of plasma ghrelin in predicting the outcome of patients with chronic heart failure. Archives of Medical Research, 45, 263–269.PubMed

53.

Khatib, M. N., Shankar, A., Kirubakaran, R., Agho, K., Simkhada, P., Gaidhane, S., et al. (2015). Effect of ghrelin on mortality and cardiovascular outcomes in experimental rat and mice models of heart failure: A systematic review and meta-analysis. PLoS ONE, 10, e0126697.PubMedPubMedCentral

54.

Pu, W. T., Ma, Q., & Izumo, S. (2003). NFAT transcription factors are critical survival factors that inhibit cardiomyocyte apoptosis during phenylephrine stimulation in vitro. Circulation Research, 92, 725–731.PubMed

55.

Tanaka, M., Ito, H., Adachi, S., Akimoto, H., Nishikawa, T., Kasajima, T., et al. (1994). Hypoxia induced apoptosis with enhanced expression of Fas antigen messenger RNA in cultured neonatal rat cardiomyocytes. Circulation Research, 75, 426–433.PubMed

56.

Venkatesan, B., Prabhu, S. D., Venkatachalam, K., Mummidi, S., Valente, A. J., Clark, R. A., et al. (2010). WNT1-inducible signaling pathway protein-1 activates diverse cell survival pathways and blocks doxorubicin-induced cardiomyocyte death. Cellular Signalling, 22, 809–820.PubMedPubMedCentral

57.

Das, J., Ghosh, J., Manna, P., & Sil, P. C. (2011). Taurine suppresses doxorubicin-triggered oxidative stress and cardiac apoptosis in rat via up-regulation of PI3-K/Akt and inhibition of p53, p38-JNK. Biochemical Pharmacology, 81, 891–899.PubMed

58.

Lee, B. S., Oh, J., Kang, S. K., Park, S., Lee, S. H., Choi, D., et al. (2015). Insulin protects cardiac myocytes from doxorubicin toxicity by Sp1-mediated transactivation of surviving. PLoS ONE. https://doi.org/10.1371/journal.pone.0135438.CrossRefPubMedPubMedCentral

59.

Yu, W., Sun, H., Zha, W., Cui, W., Xu, L., Min, Q., et al. (2017). Apigenin attenuates adriamycin-induced cardiomyocyte. Apoptosis via the PI3K/AKT/mTOR pathway. Evidence-Based Complementary and Alternative Medicine, 25, 90676. https://doi.org/10.1155/2017/2590676.CrossRef

60.

Piddo, A. M., Sánchez, M. I., Sapag-Hagar, M., Corbalán, R., Foncea, R., Ebensperger, R., et al. (1996). Cyclic AMP-dependent protein kinase and mechanical heart function in ventricular hypertrophy induced by pressure overload or secondary to myocardial infarction. Journal of Molecular and Cellular Cardiology, 28, 1073–1083.PubMed

61.

Zakhary, D. R., Moravec, C. S., Stewart, R. W., & Bond, M. (1999). Protein kinase A (PKA)-dependent troponin-I phosphorylation and PKA regulatory subunits are decreased in human dilated cardiomyopathy. Circulation, 99, 505–510.PubMed

62.

Anand, I., Ferrari, R., Kalra, G., Wahi, P., Poole-Wilson, P., & Harris, P. (1989). Edema of cardiac origin: Studies of body water and sodium, renal function, hemodynamic indexes and plasma hormones in untreated congestive cardiac failure. Circulation, 80, 299–305.PubMed

63.

Friberg, L., Werner, S., Eggertsen, G., & Ahnve, S. (2000). Growth hormone and insulin-like growth factor-1 in acute myocardial infarction. European Heart Journal, 21, 1547–1554.PubMed

64.

Langer, S. W. (2014). Dexrazoxane for the treatment of chemotherapy-related side effects. Cancer Manag Res., 6, 357–363.PubMedPubMedCentral

65.

Hasinoff, B. B., Kuschak, T. I., Yalowich, J. C., & Creighton, A. M. (1995). A QSAR study comparing the cytotoxicity and DNA topoisomerase II inhibitory effects of bisdioxopiperazine analogs of ICRF-187 (dexrazoxane). Biochemical Pharmacology, 50(7), 953–958.PubMed

66.

Holcenberg, J. S., Tutsch, K. D., Earhart, R. H., et al. (1986). Phase I study of ICRF-187 in pediatric cancer patients and comparison of its pharmacokinetics in children and adults. Cancer Treatment Reports, 70(6), 703–709.PubMed

67.

Liesmann, J., Belt, R., Haas, C., & Hoogstraten, B. (1981). Phase I evaluation of ICRF-187 (NSC-169780) in patients with advanced malignancy. Cancer, 47(8), 1959–1962.PubMed

68.

Vogel, C. L., Gorowski, E., Davila, E., et al. (1987). Phase I clinical trial and pharmacokinetics of weekly ICRF-187 (NSC 169780) infusion in patients with solid tumors. Investigational New Drugs, 5(2), 187–198.PubMed

69.

Marty, M., Espié, M., Llombart, A., Monnier, A., Rapoport, B. L., & Stahalova, V. (2006). Dexrazoxane Study Group multicenter randomized phase III study of the cardioprotective effect of dexrazoxane (Cardioxane) in advanced/metastatic breast cancer patients treated with anthracycline-based chemotherapy. Annals of Oncology, 17(4), 614–622.PubMed

70.

Mouridsen, H. T., Langer, S. W., Buter, J., et al. (2007). Treatment of anthracycline extravasation with Savene (dexrazoxane): Results from two prospective clinical multicentre studies. Annals of Oncology, 18(3), 546–550.PubMed

71.

Tebbi, C. K., London, W. B., Friedman, D., et al. (2007). Dexrazoxane-associated risk for acute myeloid leukemia/myelodysplastic syndrome and other secondary malignancies in pediatric Hodgkin’s disease. Journal of Clinical Oncology, 25, 493–500.PubMed

72.

Garin, M. C., Burns, C. M., Kaul, S., & Cappola, A. R. (2013). The human experience with ghrelin administration. Journal of Clinical Endocrinology and Metabolism, 98(5), 1826–1837.PubMedPubMedCentral

73.

Adachi, S., Takiguchi, S., Okada, K., et al. (2010). Effects of ghrelin administration after total gastrectomy: A prospective, randomized, placebo-controlled phase II study. Gastroenterology, 138, 1312–1320.PubMed

74.

Hiura, Y., Takiguchi, S., Yamamoto, K., et al. (2012). Fall in plasma ghrelin concentrations after cisplatin-based chemotherapy in esophageal cancer patients. Int J Clin Oncol., 17, 316–323.PubMed

75.

Lambert, E., Lambert, G., Ika-Sari, C., et al. (2011). Ghrelin modulates sympathetic nervous system activity and stress response in lean and overweight men. Hypertension, 58, 43–50.PubMed

76.

Vestergaard, E. T., Hansen, T. K., Gormsen, L. C., et al. (2007). Constant intravenous ghrelin infusion in healthy young men: Clinical pharmacokinetics and metabolic effects. American Journal of Physiology Endocrinology and metabolism, 292, E1829–E1836.PubMed

77.

Kluge, M., Schussler, P., Uhr, M., Yassouridis, A., & Steiger, A. (2007). Ghrelin suppresses secretion of luteinizing hormone in humans. The Journal of Clinical Endocrinology & Metabolism, 92, 3202–3205.

78.

Kluge, M., Uhr, M., Bleninger, P., Yassouridis, A., & Steiger, A. (2009). Ghrelin suppresses secretion of FSH in males. Clinical Endocrinology (Oxford), 70, 920–923.

79.

Huda, M. S., Mani, H., Dovey, T., et al. (2010). Ghrelin inhibits autonomic function in healthy controls, but has no effect on obese and vagotomized subjects. Clinical Endocrinology—Oxford, 73, 678–685.PubMed

80.

Kluge, M., Schussler, P., Bleninger, P., et al. (2008). Ghrelin alone or co-administered with GHRH or CRH increases non-REM sleep and decreases REM sleep in young males. Psychoneuroendocrinology, 33, 497–506.PubMed

Titel: Acylated Ghrelin Protects the Hearts of Rats from Doxorubicin-Induced Fas/FasL Apoptosis by Stimulating SERCA2a Mediated by Activation of PKA and Akt
verfasst von: Ali A. Shati
M. Dallak
Publikationsdatum: 15.05.2019
Verlag: Springer US
Erschienen in: Cardiovascular Toxicology / Ausgabe 6/2019
Print ISSN: 1530-7905
Elektronische ISSN: 1559-0259
DOI: https://doi.org/10.1007/s12012-019-09527-8

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Acylated Ghrelin Protects the Hearts of Rats from Doxorubicin-Induced Fas/FasL Apoptosis by Stimulating SERCA2a Mediated by Activation of PKA and Akt

Abstract

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 6/2019

Direct and Indirect Effect of Air Particles Exposure Induce Nrf2-Dependent Cardiomyocyte Cellular Response In Vitro

2,3,7,8-Tetrachlorodibenzo-p-dioxin Induces Vascular Dysfunction That is Dependent on Perivascular Adipose and Cytochrome P4501A1 Expression

Coenzyme Q10 Alleviates Chronic Nucleoside Reverse Transcriptase Inhibitor-Induced Premature Endothelial Senescence

Therapeutic Effects of Liraglutide, Oxytocin and Granulocyte Colony-Stimulating Factor in Doxorubicin-Induced Cardiomyopathy Model: An Experimental Animal Study

Intermittent Exposure to Chlorpyrifos Differentially Impacts Neuroreflex Control of Cardiorespiratory Function in Rats

MDMA Induced Cardio-toxicity and Pathological Myocardial Effects: A Systematic Review of Experimental Data and Autopsy Findings