Transient protection by peripheral benzodiazepine receptors during the early events of ultraviolet light-induced apoptosis

Pe, Stoebner; Carayon, Pierre; Casellas, Pierre; Portier, Marielle; Lavabre-Bertrand, T; Cuq, Pierre; Jp, Cano; Meynadier, J; Meunier, Lucy

doi:10.1038/sj.cdd.4400861

Cited by 47 publications

(37 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…mRNAs extracted from both cell lines, as well as from LN18 glioma cells used as positive controls, were subjected to RT-PCR (Fig. 1A) and yielded a signal for LN18 and SK-N-BE cells only, consistent with the reported absence of PBR expression in Jurkat cells [39]. These results were confirmed by immunoblotting.…”

Section: Pbr Ligands Are Toxic For Both Sk-n-be Neuroblastoma Cells Asupporting

confidence: 73%

Peripheral benzodiazepine receptor (PBR) ligand cytotoxicity unrelated to PBR expression

Hans

Wislet

Lallemend

et al. 2005

Biochemical Pharmacology

View full text Add to dashboard Cite

show abstract

Section: Pbr Ligands Are Toxic For Both Sk-n-be Neuroblastoma Cells Asupporting

confidence: 73%

Peripheral benzodiazepine receptor (PBR) ligand cytotoxicity unrelated to PBR expression

Hans

Wislet

Lallemend

et al. 2005

Biochemical Pharmacology

View full text Add to dashboard Cite

show abstract

“…The peripheral benzodiazepine receptor/ACBP complex may play a role in preventing apoptosis by stabilizing the mitochondrial membrane by ensuring an adequate supply of cholesterol (41)(42)(43). Interestingly, a correlation of breast cancer cell aggressive phenotype with peripheral benzodiazepine receptor expression in the nuclear membrane has been documented (44).…”

Section: Discussionmentioning

confidence: 99%

Dysregulation of Sterol Response Element-Binding Proteins and Downstream Effectors in Prostate Cancer during Progression to Androgen Independence

et al. 2004

View full text Add to dashboard Cite

Androgen ablation, the most common therapeutic treatment used for advanced prostate cancer, triggers the apoptotic regression of prostate tumors. However, remissions are temporary because surviving prostate cancer cells adapt to the androgen-deprived environment and form androgen-independent (AI) tumors. We hypothesize that adaptive responses of surviving tumor cells result from dysregulated gene expression of key cell survival pathways. Therefore, we examined temporal alterations to gene expression profiles in prostate cancer during progression to androgen independence at several time points using the LNCaP xenograft tumor model. Two key genes, sterol response element-binding protein (SREBP)-1 and -2 (SREBP-1a,-1c, and -2), were consistently dysregulated. These genes are known to coordinately control the expression of the groups of enzymes responsible for lipid and cholesterol synthesis. Northern blots revealed modest increased expression of SREBP-1a, -1c, and -2 after castration, and at androgen independence (day 21-28), the expression levels of both SREBP-1a and -1c were significantly greater than precastrate levels. Changes in SREBP-1 and -2 protein expression were observed by Western analysis. SREBP-1 68-kDa protein levels were maintained throughout progression, however, SREBP-2 68-kDa protein expression increased after castration and during progression (3-fold). SREBPs are transcriptional regulators of over 20 functionally related enzymes that coordinately control the metabolic pathways of lipogenesis and cholesterol synthesis, some of which were likewise dysregulated during progression to androgen independence. RNA levels of acyl-CoA-binding protein/diazepam-binding inhibitor and fatty acid synthase decreased significantly after castration, and then, during progression, increased to levels greater than or equal to precastrate levels. Expression of farnesyl diphosphate synthase did not decrease after castration but did increase significantly during progression to androgen independence. Levels of SREBP cleavageactivating protein, a regulator of SREBP transcriptional activity, decreased after castration and increased significantly at androgen independence. In clinical prostate cancer specimens from patients with varying grades of disease, the stained tissue sections showed high levels of SREBP-1 protein compared with noncancerous prostate tissue. After hormone withdrawal therapy, tumor levels of SREBP-1 decreased significantly after 6 weeks. AI tumors expressed significantly higher levels of SREBP-1. In summary, the LNCaP xenograft model of human prostate cancer as well as clinical specimens of prostate cancer demonstrated an up-regulation of SREBPs and their downstream effector genes during progression to androgen independence. As the AI phenotype emerges, enzymes critical for lipogenesis and cholesterol synthesis are activated and likely contribute significantly to cell survival of AI prostate cancer.

show abstract

“…One of these is the peripheral benzodiazepine receptor (PBR) -an 18-kDa mitochondrial membrane protein that interacts with VDAC and ANT. PBR overexpression has been shown to be cytoprotective (Stoebner et al, 2001). Hexokinase II, a mitochondrial protein that interacts with VDAC and catalyzes the first step of glycolysis, has also been shown to inhibit apoptosis.…”

Section: Bax and Bakmentioning

confidence: 99%

Chemotherapy: targeting the mitochondrial cell death pathway

2002

View full text Add to dashboard Cite

Transient protection by peripheral benzodiazepine receptors during the early events of ultraviolet light-induced apoptosis

Cited by 47 publications

References 43 publications

Peripheral benzodiazepine receptor (PBR) ligand cytotoxicity unrelated to PBR expression

Peripheral benzodiazepine receptor (PBR) ligand cytotoxicity unrelated to PBR expression

Dysregulation of Sterol Response Element-Binding Proteins and Downstream Effectors in Prostate Cancer during Progression to Androgen Independence

Chemotherapy: targeting the mitochondrial cell death pathway

Contact Info

Product

Resources

About