RESVERATROL, PALMİTAT İLE İNDÜKLENEN ENDOPLAZMİK RETİKULUM STRESİ İNHİBE EDER: ANTİ-APOPTOTİK ETKİ

Abstract

Giriş: Endoplazmik retikulum (ER) stresin obezite patofizyolojisinde yeri bilinmesine karşın, obezite ile indüklenen kardiyovasküler hastalıklarda (ER) stresin rolü tam olarak bilinmemektedir. Çalışmamız, doğal bir polifenolik bileşik olan resveratrolün H9c2 hücre dizisinde serbest yağ asidi olan palmitik asid (PA) ile indüklenen ER-stres üzerine olan etkilerini incelemek amacıyla gerçekleştirilmiştir.

Gereç ve Yöntem: H9c2 hücre dizisi çeşitli konsantrasyon ve zaman aralıklarında PA ile inkübe edilerek, ER-stres oluşumu sağlanmıştır. Resveratrolün çeşitli konsantrasyonları kullanılarak, ER-stres yolağı ve bu yolağın indükledği apoptotik yolak incelenmiştir.

Bulgular: PA doz ve süre bağımlı olarak ER-stres yolağını aktive etmiştir. Bu yolak, apoptotik bir yolağın da aktivasyonuna neden olmuştur. Resveratrol, PA ile indüklenen ER-stresi azaltmakla birlikte, apoptozu da inhibe etmiştir. Bununla birlikte, PA hücresel oksidatif stresin artmasına neden olurken, resveratrol antioksidan etkinik sergilemiştir.

Sonuç: Sonuçlarımız, H9c2 hücrelerinde PA ile indüklenen ER-stresin azaltılmasında ve apoptozun inhibe edilmesinde resveratrolün etkili olduğunu göstermiştir. 

Keywords

• Apoptoz,endoplazmik retikulum stres,H9c2 hücre dizisi,palmitik asid,resveratrol

Resveratrol Inhibits Palmitic Acid Induced Endoplasmic Reticulum Stres: Anti-Apoptotic Effect

Abstract

Introduction: Endoplasmic reticulum (ER) stress is involved in the pathophysiology of obesity but little is known about the role of ER-stress on obesity-induced cardiovascular diseases. Material and Methods: This study was designed to examine the effect of resveratrol, a natural polyphenolic compound, on palmitic acid-induced ER-stress in H9c2 cell lines. ER-stress was induced by various concentration of PA in different time manner in H9c2 cell lines. Effects of resveratrol on ER-stress and apoptosis pathways were examined in this model. Results: PA activated ER-stress pathway in a dose- and time-dependent manner. Indeed, apoptotic pathway was activated in the cells by PA. Resveratrol not only alleviated ER-stress but also inhibited apoptosis. On the other hand, PA increased oxidative stress in the cells which was alleviated by resveratrol. Conclusion: Our results suggest that, resveratrol play a role in alleviating ER-stress and inhibiting apoptosis in H9c2 cell lines.

Keywords

• Apoptosis,endoplasmic reticulum stress,H9c2 cell,palmitic acid,resveratrol

References

1. Ramalingam L, Menikdewella K, LeMieux M, et al. The renin angiotensin system, oxidative stres and mitochondrial function in obesity and insulin resistance. Biochim Biophys Acta. 2016 Aug 4. [Epub ahead of print].
2. Maroufi NF, Farzaneh K, Alibabrdel M, et al. Taq1B Polymorphism of Cholesteryl Ester Transfer Protein (CETP) and Its Effects on the Serum Lipid Levels in Metabolic Syndrome Patients. Biochem Genet. 2016. [Epub ahead of print].
3. Ceylan-Isik AF, Kandadi MR, Xu X, et al. Apelin administration ameliorates high fat diet-induced cardiac hypertrophy and contractile dysfunction. J Mol Cell Cardiol. 2013; 63: 4-13.
4. Xu X, Pang J, Chen Y, Bucala R, Zhang Y, Ren J. Macrophage migration inhibitory factor (MIF) knockout preserves cardiac homeostasis through alleviating Akt-mediated myocardial autophagy suppression in high-fat diet-induced obesity. Int J Obes. 2016; 39(3): 387-96.
5. Yalcin A, Hotamisligil GS. Impact of ER protein homeostasis on metabolism. Diabetes. 2013; 62(3): 691-3.
6. Gallagher EJ, Leroith D, Karnieli E. Insulin resistance in obesity as the underlying cause for the metabolic syndrome. Mt Sinai J Med. 2010; 77(5): 511-23. 7. Lee DK, Cheng R, Nguyen T, et al. Characterization of apelin, the ligand for the APJ receptor. J Neurochem. 2000; 74(1): 34-41.
7. Renaud J, Bournival J, Zottig X, Martinoli MG. Resveratrol protects DAergic PC12 cells from high glucose-induced oxidative stres and apoptosis: effect on p53 and GRP75 localization. Neurotox Res. 2014; 25(1): 110-23.
8. Liu MH, Lin XL, Guo DM, et al. Resveratrol protects PC12 cells from high glucose-induced neurotoxicity via PI3K/Akt/FoxO3a pathway. Cell Mol Neurobiol. 2016; 35(4): 513-22.

9. Tatlidede E, Sehirli O, Velioğlu-Oğünc A, et al. Resveratrol treatment protects against doxorubicin- induced cardiotoxicity by alleviating oxidative damage. Free Radic Res. 2009. 43(3): 195-205.
10. Huang CY, Ting WJ, Huang CY, Yang JY, Lin WT. Resveratrol attenuated hydrogen peroxide- induced myocardial apoptosis by autophagic flux. Food Nutr Res. 2016; 60: 30511.
11. Yang B, Ma S, Wang YB, et al. Resveratrol exerts protective effects on anoxia/reoxygenation injury in cardiomyocytes via miR-34a/Sirt1 signaling pathway. Eur Rev Med Pharmacol Sci. 2016; 20(12): 2734-41.
12. Gu J, Hu W, Song ZP, Chen YG, Zhang DD, Wang CQ. Resveratrol-induced autophagy promotes survival and attenuates doxorubicin-induced
13. cardiotoxicity. Int Immunopharmacol. 2016; 32: 1- 7.
14. Ozcan U, Yilmaz E, Ozcan L, et al. Chemical chaperones reduce ER-stres and restore glucose homeostasis in a mouse model of type 2 diabetes. Science. 2006. 313(5790): 1137-40.
15. Jia G, Durante W, Sowers JR. Insulin resistance and hyperinsulinaemia in diabetic cardiomyopathy. Nat Rev Endocrinol. 2016; 12(3): 144-53.
16. Cominacini L, Mozzini C, Garbin U, et al. Endoplasmic reticulum stres and Nrf2 signaling in cardiovascular diseases. Free Radic Biol Med. 2015; 88: 233-42.
17. Wu LL, Russell DL, Wong SL, et al. Mitochondrial dysfunction in oocytes of obese mothers: transmission to offspring and reversal by pharmacological endoplasmic reticulum stres inhibitors. Development. 2015; 142(4): 681-91.
18. Younce CW, Niu J, Ayala J, et al. Exendin-4 improves cardiac function in mice overexpressing monocyte
19. chemoattractant protein-1 in cardiomyocytes. J Mol Cell Cardiol. 2015; 76: 172- 6.
20. Fremont L. Biological effects of resveratrol. Life Sci. 2000: 66(8); 663-73.
21. Weiskirchen S, Weiskirchen R. Resveratrol: How Much Wine Do You Have to Drink to Stay Healthy? Adv Nutr. 2016; 7(4): 706-18.
22. Bonnefont-Rousselot D. Resveratrol and Cardiovascular Diseases. Nutrients. 2016; 8(5), 250; doi:10.3390/nu8050250.
23. Feng J, Yang Y, Zhou Y, et al. Bakuchiol attenuates myocardial ischemia reperfusion injury by maintaining mitochondrial function: the role of silent information regulator 1. Apoptosis. 2016; 21(5): 532-45.