Gene interactions and pathways from curated databases and text-mining
Eur J Pharmacol 2010, PMID: 20553909

Trichostatin a prevents TGF-beta1-induced apoptosis by inhibiting ERK activation in human renal tubular epithelial cells.

Yoshikawa, Masahiro; Hishikawa, Keiichi; Idei, Mana; Fujita, Toshiro

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.

Diseases/Pathways annotated by Medline MESH: MAP Kinase Signaling System
Document information provided by NCBI PubMed

Text Mining Data

transforming growth factor beta1 ⊣ tricostatin A (TSA): " 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 ) "

HDAC ⊣ tricostatin A (TSA): " 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 ) "

p38 ⊣ caspase-8: " 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 ) "

p38 ⊣ TSA: " 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 ) "

caspase-9 ⊣ Smad3: " 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 ) "

caspase-8 ⊣ TSA: " 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 ) "

Smad3 ⊣ TSA: " 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 ) "

p38 → TGF-beta1: " 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 ) "

caspase-9 → TGF-beta1: " 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 ) "

Smad3 → TGF-beta1: " 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 ) "

ERK ⊣ TSA: " 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 "

ERK → TGF-beta1: " 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 "

Manually curated Databases

No curated data.