Pregledni rad

Endothelin axis and apoptosis

JÓZSEF PETRIK ; Department of Medical Biochemistry and Haematology, Faculty of Pharmacy and Biochemistry, University of Zagreb, A. Kovačića 1, 10 000 Zagreb, Croatia

Sažetak

Endothelin axis (endothelin-1, -2 and -3, and endothelin receptors ETAR and ETBR) plays the key role in the various functions of the organism: acts as a modulator of vascular tone, tissue differentiation, growth and development, cell proliferation, and hormone synthesis. In addition to its physiological role, endothelin axis or individual components of the system, can have a significant effect on the tissue remodelling process and tumorigenesis. For example, endothelin-1 modulates mitosis, apoptosis and angiogenesis and can stimulate tumour invasion and metastasis. Increased endothelin-1 expression
has been demonstrated in breast, ovarian, prostate and colorectal
cancers. In tumour cells, the binding of endothelin-1 to ETA receptor induces
signalling pathway for survival. Endothelin-1 triggers the anti-apoptotic
signal through phosphatidylinositol 3-kinase (PI3-K)-dependent Akt
phosphorylation. Endothelin receptors are coupled with G-proteins and they differ in sensitivity to antagonists. G-proteins are involved in cell signalling via adenylate cyclase, ion channels, PLC, PLA2, PKC, intracellular Ca2+, calcineurin and MAP kinase. It is believed that this activity is mediated by ETAR, since the application of their specific antagonist BQ-123 causes a reverse effect. Endothelin receptor antagonists such as A-127722, BQ-123, BQ-788, etc. act specifically on either proliferation or apoptosis depending on the cell type. Today, certain endothelin receptor antagonists, such as atrasentan, are applied in the treatment of lung and prostate cancer or are at different phases of clinical trials.

Ključne riječi

Endothelin axis; apoptosis; endothelin receptor antagonists

Hrčak ID:

126353

URI

https://hrcak.srce.hr/126353

Datum izdavanja:

31.7.2014.

Posjeta: 1.051 *