Yıl: 2021 Cilt: 46 Sayı: 3 Sayfa Aralığı: 299 - 305 Metin Dili: İngilizce DOI: 10.1515/tjb-2019-0397 İndeks Tarihi: 20-02-2022

Suberoylanilide hydroxamic acid inhibits LX2 cells proliferation via decreasing yes-associated protein/transcriptional coactivator with PDZ-binding motif proteins

Öz:
Background: Hepatic fibrosis is a complex and dynamic process similar to “wound healing” that results in the pro gressive accumulation of connective tissue. We aimed to investigate the epigenetic control of liver fibrosis and Hip po pathway in human hepatic stellate cell (HSC) line. We examined the effect of Suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor on the LX2 cell line. Material and methods: 2.5 μM SAHA was treated to LX2 cell line for 2 days. Cell proliferation and apoptosis measurement were performed by Muse Cell Analyzer. Yes-Associated Protein/Transcrıptional Coactivator With Pdz-Binding Motif (YAP/TAZ) and alpha-smooth muscle actin (α-SMA) protein expression levels were measured by western blotting. Results: In our study, we observed that the SAHA treatment reduced cell viability and induced apoptosis of LX2 cells statistically. We found that SAHA treatment decreased α-SMA, YAP and TAZ proteins levels statistically. Conclusion: Decreased cell viability could be due to physiological, autophagical and also related to the apop totical mechanisms. We thought that SAHA plays an important role in the creation of the fates of the LX2 cell line.
Anahtar Kelime:

Suberoylanilid hidroksamik asit, PDZ bağlayıcı motif proteinleri ile yes ilişkili protein/ transkripsiyonel koaktivatör azaltarak LX2 hücrelerinin proliferasyonunu inhibe eder

Öz:
Amaç: Hepatik fibrozis, bağ dokusunun birikimi ile sonuçlanan “yara iyileşmesine” benzer karmaşık ve dina mik bir süreçtir. Bu çalışmada, insan hepatik stellat hücre (HSC) hattında karaciğer fibrozisinin ve Hippo yolağının epigenetik kontrolünü araştırmayı amaçladık. Histon dea setilaz inhibitörü olan Suberoylanilid hidroksamik asit (SAHA)’nın LX2 hücre hattı üzerindeki etkisini inceledik. Materyal ve metod: LX2 hücrelerine 2 gün süreyle 2.5 μM SAHA uygulandı. Hücre proliferasyonu ve apoptoz ölçüm leri, Muse Cell Analyzer cihazı ile gerçekleştirildi. Yes-asso ciated protein/ transcriptional coactivator with PDZ-binding motif protein (YAP/TAZ) ve α-düz kas aktin (α-SMA) protein ekspresyon seviyeleri, western blot analizi ile belirlendi. Bulgular: Çalışmamızda SAHA’nın, hücre canlılığını azalttığını ve LX2 hücrelerinin apopitozunu istatistiksel olarak indüklediğini gözlemledik. SAHA ‘nın α-SMA, YAP ve TAZ protein düzeylerini istatistiksel olarak düşürdüğünü bulduk. Sonuç: Hücre canlılığının azalması; fizyolojik, otofajik ve aynı zamanda apoptotik mekanizmalardan kaynaklanabilir. SAHA’nın LX2 hücrelerinin kaderinin belirlenmesinde önemli bir rol oynadığını düşünmekteyiz.
Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
  • 1. Dong X, Weng Z. The correlation between histone modifications and gene expression. Epigenomics 2013;5:113–6.
  • 2. Mottet D, Castronovo V. Histone deacetylases: target enzymes for cancer therapy. Clin Exp Metastasis 2008;25:183–9.
  • 3. Bannister AJ , Kouzarides, T. Regulation of chromatin by histone modifications. Cell Res 2011;21:381–395.
  • 4. Lakshmaiah KC, Jacob LA, Aparna S, Lokanatha D, Saldanha SC. Epigenetic therapy of cancer with histone deacetylase inhibitors. J Cancer Res Ther 2014;10:469–78.
  • 5. Lane AA, Chabner BA. Histone deacetylase inhibitors in cancer therapy. J Clin Oncol 2009;27:5459–68.
  • 6. Parbin S, Kar S, Shilpi A, Sengupta, D, Deb M. Histone deacetylases a saga of perturbed acetylation homeostasis in cancer. J Histochem Cytochem 2014;62:11–33.
  • 7. Marks PA. Histone deacetylase inhibitors: a chemical genetics approach to understanding cellular functions. Biochim Biophys Acta 2010;1799:717–725.
  • 8. Wang W, Yan M, Ji Q, Lu J, Ji Y, Ji J. Suberoylanilide hydroxamic acid suppresses hepatic stellate cells activation by HMGB1 dependent reduction of NF-κB1. Peer J 2015;3:e1362.
  • 9. Meng Z, Moroishi T, Guan KL. Mechanisms of hippo pathway regulation. Genes Dev 2016;30:1–17.
  • 10. Yu X, Guan KL. The Hippo pathway: regulators and regulations. Genes Dev 2013;27:355–71.
  • 11. Warren JSA, Xiao Y, Lamar JM. YAP/TAZ activation as a target for treating metastatic cancer. Cancers (Basel) 2018;10 pii:E115.
  • 12. Zhao B, Ye X, Yu J, Li L, Li W, Li S, et al. TEAD mediates YAPdependent gene induction and growth control. Genes Dev 2008; 22:1962–71.
  • 13. Mannaerts I, Leite SB, Verhulst S, Claerhout S, Eysackers, N, et al. J Hepatol 2015;63:679–88.
  • 14. Juan WC, Hong W. Targeting the hippo signaling pathway for tissue regeneration and cancer therapy genes. Genes 2016;7. pii: E55.
  • 15. Park KC, Park JH, Jeon JY, Kim SY, Kim JM, Lim CY, Lee TH, Kim HK, Lee HG, Kim SM, Kwon HJ, Suh JS, Kim SW, Choi SH. A new histone deacetylase inhibitor improves liver fibrosis in BDL rats through suppression of hepatic stellate cells. Br J Pharmacol 2014;171: 4820–30.
  • 16. White SM, Murakami S, Yi C. The complex entanglement of HippoYap/Taz signaling in tumor immunity. Oncogene 2019. https:// doi.org/10.1038/s41388-018-0649-6.
  • 17. Zhang X, Zhao H, Li Y, Xia D, Yang L, et al. The role of YAP/TAZ activity in cancer metabolic reprogramming. Mol Cancer 2018;17: 134.
  • 18. Kim W, Khan SK, Liu Y, Xu, R, Park, O, et al. Hepatic Hippo signaling inhibits protumoural microenvironment to suppress hepatocellular carcinoma. Gut 2018;67:1692–703.
  • 19. Moya IM, Halder G. Hippo-YAP/TAZ signalling in organ regeneration and regenerative medicine. Nat Rev Mol Cell Biol 2018. https://doi.org/10.1038/s41580-018-0086-y.
  • 20. Konishi T, Schuster RM, Lentsch AB. Proliferation of hepatic stellate cells, mediated by YAP and TAZ, contributes to liver repair and regeneration after liver ischemia-reperfusion injury. Am J Physiol Gastrointest Liver Physiol 2018;314:471–82.
  • 21. Machado MV, Michelotti GA, Pereira TA, Xie G, Premont R, et al. Accumulation of duct cells with activated YAP parallels fibrosis progression in non-alcoholic fatty liver disease. J Hepatol 2015; 63:962–70.
  • 22. Szeto SG, Narimatsu M, Lu M, He X, Sidiqi AM, et al. YAP/TAZ are mechanoregulators of TGF-β-smad signaling and renal fibrogenesis. J Am Soc Nephrol 2016;27:3117–28.
  • 23. Noguchi S, Saito A, Nagase T. YAP/TAZ signaling as a molecular link between fibrosis and cancer. Int J Mol Sci 2018;19. pii:E3674.
  • 24. Wang X, Zheng Z, Caviglia JM, Corey KE, Herfel, et al. Hepatocyte TAZ/WWTR1 promotes inflammation and fibrosis in nonalcoholic steatohepatitis. Cell Metab 2016;24:848–62.
  • 25. Zhang K, Chang Y, Shi Z, Han X, Han Y, et al. ω-3 PUFAs ameliorate liver fibrosis and inhibit hepatic stellate cells proliferation and activation by promoting YAP/TAZ degradation. Sci Rep 2016;6: 30029.
  • 26. Du K, Hyun J, Premont RT, Choi SS, Michelotti GA, et al YAP signaling pathway regulates glutaminolysis to control activation of hepatic stellate cells. Gastroenterology 2013;154:1465–79.
  • 27. Herrera J, Henke CA, Bitterman PB. Extracellular matrix as a driver of progressive fibrosis. J Clin Investing 2018;128:45–53.
  • 28. Bertero T, Cottrill KA, Annis S, Bhat B, Gochuico BR, et al YAP/TAZmiR-130/301 molecular circuit exerts systems-level control of fibrosis in a network of human diseases and physiologic conditions. Sci Rep 2015;5:18277-92.
  • 29. Perumal N, Perumal M, Halagowder D, Sivasithamparam N. Morin attenuates diethylnitrosamine-induced rat liver fibrosis and hepatic stellate cell activation by co-ordinated regulation of Hippo/Yap and TGF-β1/Smad signaling. Biochimie 2017;140: 10–9.
APA Özel M, GÜÇLÜ K, HELVACI N, KILIÇ E, Başkol M, baskol g (2021). Suberoylanilide hydroxamic acid inhibits LX2 cells proliferation via decreasing yes-associated protein/transcriptional coactivator with PDZ-binding motif proteins. , 299 - 305. 10.1515/tjb-2019-0397
Chicago Özel Merve,GÜÇLÜ Kenan,HELVACI Nazlı,KILIÇ Eser,Başkol Mevlüt,baskol gulden Suberoylanilide hydroxamic acid inhibits LX2 cells proliferation via decreasing yes-associated protein/transcriptional coactivator with PDZ-binding motif proteins. (2021): 299 - 305. 10.1515/tjb-2019-0397
MLA Özel Merve,GÜÇLÜ Kenan,HELVACI Nazlı,KILIÇ Eser,Başkol Mevlüt,baskol gulden Suberoylanilide hydroxamic acid inhibits LX2 cells proliferation via decreasing yes-associated protein/transcriptional coactivator with PDZ-binding motif proteins. , 2021, ss.299 - 305. 10.1515/tjb-2019-0397
AMA Özel M,GÜÇLÜ K,HELVACI N,KILIÇ E,Başkol M,baskol g Suberoylanilide hydroxamic acid inhibits LX2 cells proliferation via decreasing yes-associated protein/transcriptional coactivator with PDZ-binding motif proteins. . 2021; 299 - 305. 10.1515/tjb-2019-0397
Vancouver Özel M,GÜÇLÜ K,HELVACI N,KILIÇ E,Başkol M,baskol g Suberoylanilide hydroxamic acid inhibits LX2 cells proliferation via decreasing yes-associated protein/transcriptional coactivator with PDZ-binding motif proteins. . 2021; 299 - 305. 10.1515/tjb-2019-0397
IEEE Özel M,GÜÇLÜ K,HELVACI N,KILIÇ E,Başkol M,baskol g "Suberoylanilide hydroxamic acid inhibits LX2 cells proliferation via decreasing yes-associated protein/transcriptional coactivator with PDZ-binding motif proteins." , ss.299 - 305, 2021. 10.1515/tjb-2019-0397
ISNAD Özel, Merve vd. "Suberoylanilide hydroxamic acid inhibits LX2 cells proliferation via decreasing yes-associated protein/transcriptional coactivator with PDZ-binding motif proteins". (2021), 299-305. https://doi.org/10.1515/tjb-2019-0397
APA Özel M, GÜÇLÜ K, HELVACI N, KILIÇ E, Başkol M, baskol g (2021). Suberoylanilide hydroxamic acid inhibits LX2 cells proliferation via decreasing yes-associated protein/transcriptional coactivator with PDZ-binding motif proteins. Türk Biyokimya Dergisi, 46(3), 299 - 305. 10.1515/tjb-2019-0397
Chicago Özel Merve,GÜÇLÜ Kenan,HELVACI Nazlı,KILIÇ Eser,Başkol Mevlüt,baskol gulden Suberoylanilide hydroxamic acid inhibits LX2 cells proliferation via decreasing yes-associated protein/transcriptional coactivator with PDZ-binding motif proteins. Türk Biyokimya Dergisi 46, no.3 (2021): 299 - 305. 10.1515/tjb-2019-0397
MLA Özel Merve,GÜÇLÜ Kenan,HELVACI Nazlı,KILIÇ Eser,Başkol Mevlüt,baskol gulden Suberoylanilide hydroxamic acid inhibits LX2 cells proliferation via decreasing yes-associated protein/transcriptional coactivator with PDZ-binding motif proteins. Türk Biyokimya Dergisi, vol.46, no.3, 2021, ss.299 - 305. 10.1515/tjb-2019-0397
AMA Özel M,GÜÇLÜ K,HELVACI N,KILIÇ E,Başkol M,baskol g Suberoylanilide hydroxamic acid inhibits LX2 cells proliferation via decreasing yes-associated protein/transcriptional coactivator with PDZ-binding motif proteins. Türk Biyokimya Dergisi. 2021; 46(3): 299 - 305. 10.1515/tjb-2019-0397
Vancouver Özel M,GÜÇLÜ K,HELVACI N,KILIÇ E,Başkol M,baskol g Suberoylanilide hydroxamic acid inhibits LX2 cells proliferation via decreasing yes-associated protein/transcriptional coactivator with PDZ-binding motif proteins. Türk Biyokimya Dergisi. 2021; 46(3): 299 - 305. 10.1515/tjb-2019-0397
IEEE Özel M,GÜÇLÜ K,HELVACI N,KILIÇ E,Başkol M,baskol g "Suberoylanilide hydroxamic acid inhibits LX2 cells proliferation via decreasing yes-associated protein/transcriptional coactivator with PDZ-binding motif proteins." Türk Biyokimya Dergisi, 46, ss.299 - 305, 2021. 10.1515/tjb-2019-0397
ISNAD Özel, Merve vd. "Suberoylanilide hydroxamic acid inhibits LX2 cells proliferation via decreasing yes-associated protein/transcriptional coactivator with PDZ-binding motif proteins". Türk Biyokimya Dergisi 46/3 (2021), 299-305. https://doi.org/10.1515/tjb-2019-0397