Thromboxanes: Selective Biosynthesis and Distinct Biological Properties

Abstract

The prostaglandin endoperoxide ring structure alone does not establish suitability as a substrate for thromboxane synthetase, but the degree of unsaturation and carbon chain length are also essential features. Thus, human platelet microsomes can synthesize thromboxane A2, thromboxane A3, but not thromboxane A1 from their respective endoperoxides. The potent vasoconstrictor property of thromboxanes can be dissociated from its capacity to produce platelet aggregation. Furthermore, thromboxane formation is not an essential process in platelet aggregation. The observations indicate the remarkable structural specificity of both the synthetic enzymes, cyclooxygenase and thromboxane synthetase, as well as the vascular and platelet receptor sites.

Activation of thromboxane receptor α induces expression of cyclooxygenase-2 through multiple signaling pathways in A549 human lung adenocarcinoma cells

“…TXB 2 and PGE 2 in the medium were quantified with ELISA as described under MATERIALS AND METHODS. Fold increase (Fold/Basal) in PGE 2 Cells were serum-starved for 16 h and then treated with 50 nM I-BOP or vehicle for varying length of time as indicated. The cell lysates were subjected to 12% SDS-PAGE and proteins were transferred to PVDF membranes for Western blotting analysis using antibodies against each phosphorylated signaling molecules as described under MATERIALS AND METHODS.…”

“…The roles of TXA 2 in pulmonary and cardiovascular functions have been well described [2,3]. However, its role in lung tumorigenesis is less clear although it induces mitogenesis and hypertrophy of smooth muscle cells and other types of cells as described above.…”

“…Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. aggregatory activity and smooth muscle constrictive activity [2,3], which are mediated by the activation of TXA 2 receptors (TPs) [4]. Two isoforms of TP, TPα and TPβ, have been identified [5].…”

“…The role of TPs in tumorigenesis has emerged. Over the last decade, an increased interest in the role of COX-2, a rate-limiting enzyme in PGE 2 and TXA 2 biosynthesis, in tumorigenesis becomes apparent. This interest was sparked by the fact that COX inhibitors reduced the mortality rate from certain cancer patients [16,17] and that most of the tumors exhibited overexpression of COX-2, a potential oncogene [18].…”

“…This interest was sparked by the fact that COX inhibitors reduced the mortality rate from certain cancer patients [16,17] and that most of the tumors exhibited overexpression of COX-2, a potential oncogene [18]. One of the major COX-2 derived products, PGE 2 , has also been shown to induce the growth, migration, and invasiveness of carcinoma cells [19]. In view of the fact that PGE 2 up-regulates the expression of COX-2 in several cancer cell lines resulting in positive feedback actions of PGE 2 [20,21], we hypothesize that another COX-2 derived down-stream product with similar mitogenic activity, TXA 2 , will be also capable of inducing the expression of COX-2.…”