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Role of MAP kinases and their cross-talk in TGF-beta1-induced apoptosis in FaO rat hepatoma cell line.
Hepatology 2002; 35(6):1360-71Hep

Abstract

Transforming growth factor (TGF) beta1 is a potent inducer of apoptosis in the liver. During TGF-beta1-induced apoptosis, 3 mitogen-activated protein (MAP) kinases (extracellular signal-regulated kinase [ERK], c-Jun N-terminal kinase [JNK], and p38 kinase) showed simultaneously sustained activation in FaO rat hepatoma cells. TGF-beta1-induced apoptosis was markedly enhanced when ERK activation was selectively inhibited by the mitogen-activated protein kinase/extracellular signal-regulated kinase kinase inhibitor PD98059. In contrast, both interfering with p38 activity by overexpression of the dominant negative (DN) MKK6 mutant and inhibition of the JNK pathway by overexpression of the DN SEK1 mutant resulted in suppression of mitochondrial cytochrome c release, abrogating TGF-beta1-induced apoptosis. In addition, antiapoptotic Bcl-2 blocked mitochondrial cytochrome c release, suppressing TGF-beta1-induced activation of JNK and p38. Inhibition of ERK activity enhanced TGF-beta1-induced p38 and JNK activation. However, inhibition of the JNK pathway suppressed p38 but induced transient ERK activation. Similarly, interfering with the p38 pathway also attenuated JNK activation but generated transient ERK activation in response to TGF-beta1. These results indicate that disrupting one MAP kinase pathway affects the TGF-beta1-induced activation of other MAP kinases, suggesting cross-talk among MAP kinase pathways. In conclusion, we propose that the balance and integration of MAP kinase signaling may regulate commitment to TGF-beta1-induced apoptosis modulating the release of cytochrome c from mitochondria.

Authors+Show Affiliations

Laboratory of Endocrinology, Institute for Medical Sciences, Ajou University School of Medicine, Suwon, Korea.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

12029621

Citation

Park, Hyun-Jin, et al. "Role of MAP Kinases and Their Cross-talk in TGF-beta1-induced Apoptosis in FaO Rat Hepatoma Cell Line." Hepatology (Baltimore, Md.), vol. 35, no. 6, 2002, pp. 1360-71.
Park HJ, Kim BC, Kim SJ, et al. Role of MAP kinases and their cross-talk in TGF-beta1-induced apoptosis in FaO rat hepatoma cell line. Hepatology. 2002;35(6):1360-71.
Park, H. J., Kim, B. C., Kim, S. J., & Choi, K. S. (2002). Role of MAP kinases and their cross-talk in TGF-beta1-induced apoptosis in FaO rat hepatoma cell line. Hepatology (Baltimore, Md.), 35(6), pp. 1360-71.
Park HJ, et al. Role of MAP Kinases and Their Cross-talk in TGF-beta1-induced Apoptosis in FaO Rat Hepatoma Cell Line. Hepatology. 2002;35(6):1360-71. PubMed PMID: 12029621.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of MAP kinases and their cross-talk in TGF-beta1-induced apoptosis in FaO rat hepatoma cell line. AU - Park,Hyun-Jin, AU - Kim,Byung-Chul, AU - Kim,Seong-Jin, AU - Choi,Kyeong Sook, PY - 2002/5/25/pubmed PY - 2002/6/22/medline PY - 2002/5/25/entrez SP - 1360 EP - 71 JF - Hepatology (Baltimore, Md.) JO - Hepatology VL - 35 IS - 6 N2 - Transforming growth factor (TGF) beta1 is a potent inducer of apoptosis in the liver. During TGF-beta1-induced apoptosis, 3 mitogen-activated protein (MAP) kinases (extracellular signal-regulated kinase [ERK], c-Jun N-terminal kinase [JNK], and p38 kinase) showed simultaneously sustained activation in FaO rat hepatoma cells. TGF-beta1-induced apoptosis was markedly enhanced when ERK activation was selectively inhibited by the mitogen-activated protein kinase/extracellular signal-regulated kinase kinase inhibitor PD98059. In contrast, both interfering with p38 activity by overexpression of the dominant negative (DN) MKK6 mutant and inhibition of the JNK pathway by overexpression of the DN SEK1 mutant resulted in suppression of mitochondrial cytochrome c release, abrogating TGF-beta1-induced apoptosis. In addition, antiapoptotic Bcl-2 blocked mitochondrial cytochrome c release, suppressing TGF-beta1-induced activation of JNK and p38. Inhibition of ERK activity enhanced TGF-beta1-induced p38 and JNK activation. However, inhibition of the JNK pathway suppressed p38 but induced transient ERK activation. Similarly, interfering with the p38 pathway also attenuated JNK activation but generated transient ERK activation in response to TGF-beta1. These results indicate that disrupting one MAP kinase pathway affects the TGF-beta1-induced activation of other MAP kinases, suggesting cross-talk among MAP kinase pathways. In conclusion, we propose that the balance and integration of MAP kinase signaling may regulate commitment to TGF-beta1-induced apoptosis modulating the release of cytochrome c from mitochondria. SN - 0270-9139 UR - https://www.unboundmedicine.com/medline/citation/12029621/Role_of_MAP_kinases_and_their_cross_talk_in_TGF_beta1_induced_apoptosis_in_FaO_rat_hepatoma_cell_line_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0270913902833572 DB - PRIME DP - Unbound Medicine ER -