Loss of prostaglandin D2 synthase: a key molecular event in the transition of a low-grade astrocytoma to an anaplastic astrocytoma

Payne, Cathy A.; Maleki, Saeed; Messina, Marinella; O'Sullivan, Maree; Stone, Graham N.; Hall, Nathan R.; Parkinson, Jonathan; Wheeler, Helen; Cook, Raymond; Biggs, Michael T.; Little, Nicholas; Teo, Charles; Robinson, Bruce G.; McDonald, Kerrie L.

doi:10.1158/1535-7163.mct-08-0629

Cited by 25 publications

(19 citation statements)

References 39 publications

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“…PGD2 is synthesized by hematopoietic PGD synthase or PTGDS. Both PTGDS and TBXAS1 are regulated by DNA methylation [28,29]. We found the hypomethylation and upregulation of both enzymes by 5-AZA in different cells and mice, which agrees with previous reports.…”

Section: Discussionsupporting

confidence: 93%

Metabolomic analysis revealed the role of DNA methylation in the balance of arachidonic acid metabolism and endothelial activation

Xue

Zhang

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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Section: Discussionsupporting

confidence: 93%

Metabolomic analysis revealed the role of DNA methylation in the balance of arachidonic acid metabolism and endothelial activation

Xue

Zhang

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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“…This might be surprising insofar as PGD 2 and its final metabolite 15deoxyD 12-14 PGJ 2 are implicated in the onset of apoptosis, through the activation of DP receptors or of PPARg 26 or of other targets. 19 Payne et al 35 also reported that L-PGDS loss was observed during transition from low grade to higher grade astrocytomas and was correlated to a poorer survival. However, our results demonstrate that PGD 2 is not an absolute antiapoptotic compound, but rather a competitive inhibitor of PGE 2 in Bax activation, as it does not preclude the Bid-induced activation of Bax.…”

Section: Discussionmentioning

confidence: 97%

Prostaglandins antagonistically control Bax activation during apoptosis

et al. 2010

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The Bax protein (Bcl-2-associated X protein) is pivotal for the apoptotic process. Bax, which resides in an inactive form in the cytosol of healthy cells, is activated during the early stages of apoptosis and becomes associated with mitochondria through poorly understood mechanisms. In this study, we show that a family of bioactive lipids, namely prostaglandins, regulates Bax-dependent apoptosis. The prostaglandin E 2 (PGE 2 ) or its derivative PGA 2 binds to Bax, induces its change of conformation, and thereby triggers apoptosis. A cysteine present in the loop between the two transmembrane a-helices of Bax, Cys126 is critical for its activation. PGD 2 inhibits PGE 2 binding to Bax and PGE 2 -induced apoptosis, as well as cell death induced by staurosporine and UV-B in various cell lines. This result is consistent with the fact that apoptosis is accompanied during these treatments by an increase in PGE 2 . This process is distinct, yet cooperative, from that involving the BH3-only protein Bid. Our results establish that the PGE 2 /PGD 2 balance is involved in a new early mechanism of control in the activation of Bax during apoptosis. Cell Death and Differentiation (2011) 18, 528-537; doi:10.1038/cdd.2010.128; published online 22 October 2010Members of the Bcl-2 (Bcl-2-associated X protein) family of proteins determine both the initiation and the execution of mitochondrial outer membrane permeabilization (MOMP) and the subsequent apoptosis. These proteins share a similar solution structure, and are subdivided into two groups: antiapoptotic proteins (e.g., Bcl-2, Bcl-Xl, Bcl-W and Mcl-1) and proapoptotic proteins, which control apoptosis through complex interaction with each other. Proapoptotic proteins are further subdivided into multidomain proteins (namely, Bax, Bak and Bok) and BH3-only proteins (e.g., Bim, Bad, Bid, Puma or Noxa) whose homology with Bcl-2 is limited to the BH3 domain. BH3-only proteins function as upstream sensors that selectively respond to specific signals and promote the proapoptotic function of Bax and/or Bak. Both in vivo and in vitro experiments have proved that the conformation of monomeric Bax/Bak change upon induction of apoptosis, leading to their oligomerization in the mitochondrial membrane and MOMP. [1][2][3] How Bax and Bak are activated is a matter of debate. 2,4 A widely accepted model proposes that some BH3-only proteins called 'activators' (tBid, Bim and Puma) induce the Bax/Bak apoptotic conformational change through transient physical interaction in a 'hit and run' manner. Another group named 'enabler' (also called derepressor or sensitizer) can release Bax and Bak from antiapoptotic proteins, which in turn trigger MOMP. [1][2][3] The existence of a direct interaction of Bax/Bak with BH3-only proteins has been challenged, suggesting the existence of alternative mechanisms responsible for the activation of Bax or Bak. A change in pH or temperature has also been shown to facilitate the transition between the inactive and active states of Bax, supporting a role for nonprotein...

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“…Reduction of ß-trace protein is a significant biological event involved in the malignant progression of astrocytoma and is predictive of poor survival (35). Significant reduction in cell proliferation and viability in the A172 glioblastoma cell line was found when PGD 2 was exogenously supplied.…”

Section: ------------------------------------------------------------mentioning

confidence: 99%

Exposure to wireless phone emissions and serum β-trace protein

Hardell¹

2010

Int J Mol Med

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Abstract. The lipocalin type of prostaglandin D synthase or ß-trace protein is synthesized in the choroid plexus, leptomeninges and oligodendrocytes of the central nervous system and is secreted into the cerebrospinal fluid. ß-trace protein is the key enzyme in the synthesis of prostaglandin D2, an endogenous sleep-promoting neurohormone in the brain. Electromagnetic fields (EMF) in the radio frequency (RF) range have in some studies been associated with disturbed sleep. We studied the concentration of ß-trace protein in blood in relation to emissions from wireless phones. This study included 62 persons aged 18-30 years. The concentration of ß-trace protein decreased with increasing number of years of use of a wireless phone yielding a negative ß coefficient = -0.32, 95% confidence interval -0.60 to -0.04. Also cumulative use in hours gave a negative ß coefficient, although not statistically significant. Of the 62 persons, 40 participated in an experimental study with 30 min exposure to an 890-MHz GSM signal. No statistically significant change of ß-trace protein was found. In a similar study of the remaining 22 participitants with no exposure, ß-trace protein increased significantly over time, probably due to a relaxed situation. EMF emissions may down-regulate the synthesis of ß-trace protein. This mechanism might be involved in sleep disturbances reported in persons exposed to RF fields. The results must be interpreted with caution since use of mobile and cordless phones were self-reported. Awareness of exposure condition in the experimental study may have influenced ß-trace protein concentrations.

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Loss of prostaglandin D2 synthase: a key molecular event in the transition of a low-grade astrocytoma to an anaplastic astrocytoma

Cited by 25 publications

References 39 publications

Metabolomic analysis revealed the role of DNA methylation in the balance of arachidonic acid metabolism and endothelial activation

Metabolomic analysis revealed the role of DNA methylation in the balance of arachidonic acid metabolism and endothelial activation

Prostaglandins antagonistically control Bax activation during apoptosis

Exposure to wireless phone emissions and serum β-trace protein

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