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Trichostatin a prevents TGF-beta1-induced apoptosis by inhibiting ERK activation in human renal tubular epithelial cells.
Eur J Pharmacol. 2010 Sep 10; 642(1-3):28-36.EJ

Abstract

Histone deacetylase (HDAC) inhibitors have recently been reported to have possible reno-protective effects in the last few years. In this study, we found that tricostatin A (TSA), an HDAC inhibitor, prevented transforming growth factor beta1 (TGF-beta1)-induced apoptosis in cultured human renal proximal tubular epithelial cells (RPTECs). TGF-beta1-induced apoptosis via the activation of both caspase-8 and caspase-9 but did not activate the Fas receptor and did not alter Bcl-2 or Bax protein expression. TSA prevented TGF-beta1-induced apoptosis and the activation of caspase-8 and caspase-9 in RPTECs but did not inhibit the TGF-beta1-induced phosphorylation of Smad3 and p38 mitogen-activated protein kinase (MAPK). However, TSA inhibited the TGF-beta1-induced phosphorylation of extracellular signal regulated kinase (ERK), and the MAPK/ERK kinase inhibitor U0126, which specifically inhibits ERK, also prevented TGF-beta1-induced apoptosis. Our results show, for the first time, that TSA inhibits TGF-beta1-induced ERK activation and overrides pro-apoptotic signals like Smad3 and p38 in human RPTECs.

Authors+Show Affiliations

Department of Internal Medicine, Division of Nephrology and Endocrinology, Graduate School of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8655, Japan.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20553909

Citation

Yoshikawa, Masahiro, et al. "Trichostatin a Prevents TGF-beta1-induced Apoptosis By Inhibiting ERK Activation in Human Renal Tubular Epithelial Cells." European Journal of Pharmacology, vol. 642, no. 1-3, 2010, pp. 28-36.
Yoshikawa M, Hishikawa K, Idei M, et al. Trichostatin a prevents TGF-beta1-induced apoptosis by inhibiting ERK activation in human renal tubular epithelial cells. Eur J Pharmacol. 2010;642(1-3):28-36.
Yoshikawa, M., Hishikawa, K., Idei, M., & Fujita, T. (2010). Trichostatin a prevents TGF-beta1-induced apoptosis by inhibiting ERK activation in human renal tubular epithelial cells. European Journal of Pharmacology, 642(1-3), 28-36. https://doi.org/10.1016/j.ejphar.2010.05.055
Yoshikawa M, et al. Trichostatin a Prevents TGF-beta1-induced Apoptosis By Inhibiting ERK Activation in Human Renal Tubular Epithelial Cells. Eur J Pharmacol. 2010 Sep 10;642(1-3):28-36. PubMed PMID: 20553909.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Trichostatin a prevents TGF-beta1-induced apoptosis by inhibiting ERK activation in human renal tubular epithelial cells. AU - Yoshikawa,Masahiro, AU - Hishikawa,Keiichi, AU - Idei,Mana, AU - Fujita,Toshiro, Y1 - 2010/06/08/ PY - 2009/10/15/received PY - 2010/05/06/revised PY - 2010/05/31/accepted PY - 2010/6/18/entrez PY - 2010/6/18/pubmed PY - 2010/10/29/medline SP - 28 EP - 36 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 642 IS - 1-3 N2 - Histone deacetylase (HDAC) inhibitors have recently been reported to have possible reno-protective effects in the last few years. In this study, we found that tricostatin A (TSA), an HDAC inhibitor, prevented transforming growth factor beta1 (TGF-beta1)-induced apoptosis in cultured human renal proximal tubular epithelial cells (RPTECs). TGF-beta1-induced apoptosis via the activation of both caspase-8 and caspase-9 but did not activate the Fas receptor and did not alter Bcl-2 or Bax protein expression. TSA prevented TGF-beta1-induced apoptosis and the activation of caspase-8 and caspase-9 in RPTECs but did not inhibit the TGF-beta1-induced phosphorylation of Smad3 and p38 mitogen-activated protein kinase (MAPK). However, TSA inhibited the TGF-beta1-induced phosphorylation of extracellular signal regulated kinase (ERK), and the MAPK/ERK kinase inhibitor U0126, which specifically inhibits ERK, also prevented TGF-beta1-induced apoptosis. Our results show, for the first time, that TSA inhibits TGF-beta1-induced ERK activation and overrides pro-apoptotic signals like Smad3 and p38 in human RPTECs. SN - 1879-0712 UR - https://www.unboundmedicine.com/medline/citation/20553909/Trichostatin_a_prevents_TGF_beta1_induced_apoptosis_by_inhibiting_ERK_activation_in_human_renal_tubular_epithelial_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(10)00506-6 DB - PRIME DP - Unbound Medicine ER -