JavaScript NENÍ povolen !

* Zobrazit nápovědu

MeSH: protein X asociovaný s bcl-2-účinky léků

2 záznamů v PubMed Filtry

Článek

DNA damage, DNA repair rates and mRNA expression levels of cell cycle genes (TP53, p21(CDKN1A), BCL2 and BAX) with respect to occupational exposure to styrene

Carcinogenesis. 2011 Jan ; 32 (1) : 74-9. [epub] 20101021

ISSN 1460-2180 | 0143-3334
Zdroj

We studied the relationship between DNA damage, DNA repair rates and messenger RNA (mRNA) expression levels of cell cycle genes TP53, p21(CDKN1A), BCL2 and BAX in a group of 71 styrene-exposed workers and 51 control individuals. The exposure was assessed by measuring the concentration of styrene at workplace and in blood. Parameters of DNA damage [measured as single-strand breaks (SSBs) and endonuclease III-sensitive sites], γ-irradiation-specific DNA repair rates and mRNA levels of studied genes were analyzed in peripheral blood lymphocytes. The workers were divided into low (<50 mg/m³) and high (>50 mg/m³) styrene exposure groups. We found negative correlations between mRNA expression of TP53, BCL2, BAX and styrene exposure (P < 0.001 for all parameters). In contrast, p21(CDKN1A) mRNA expression significantly increased with increasing styrene exposure (P = 0.001). SSBs and endonuclease III-sensitive sites increased with increasing mRNA levels of TP53 (P < 0.001 for both) and BCL2 (P = 0.038, P = 0.002, respectively), whereas the same parameters decreased with increasing mRNA levels of p21(CDKN1A) (P < 0.001, P = 0.007, respectively). γ-Irradiation-specific DNA repair rates increased with p21(CDKN1A) mRNA levels up to the low exposure level (P = 0.044). Our study suggests a possible relationship between styrene exposure, DNA damage and transcript levels of key cell cycle genes.

Článek

Transforming growth factor-beta1 inhibits all-trans retinoic acid-induced apoptosis

Leukemia research. 2006 May ; 30 (5) : 607-23. [epub] 20051019

Leuk Res
ISSN 0145-2126
Zdroj

The interaction between retinoids and transforming growth factor-beta1 (TGF-beta1) leading to regulation of proliferation, differentiation and apoptosis is not still fully understood. In this study, we demonstrated that a combination treatment with all-trans retinoic acid (ATRA) and TGF-beta1 led to the enhancement of ATRA-induced suppression of cell proliferation, which is accompanied by inhibition of ATRA-induced apoptosis in human leukemia HL-60 cells. This effect was preceded by the arrest of cells in G0/G1 cell cycle phase linked with pRb protein dephosphorylation, continuous accumulation of p21 and transiently increased level of p27, inhibitors of cyclin-dependent kinases. Inhibition of ATRA-induced apoptosis by TGF-beta1 was associated with an increased level of Mcl-1 protein, an anti-apoptotic member of Bcl-2 family, but not with inhibition of mitochondrial membrane depolarization. Levels of other Bcl-2 family proteins (Bcl-2, Bcl-X(L), Bad, Bak, Bax) were unaffected by simultaneous ATRA and TGF-beta1 treatment, when compared to ATRA alone. Upregulation of c-FLIP(L) protein, an inhibitor of apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), correspond with inhibition of ATRA-induced (autocrine TRAIL-mediated) caspase-8 activation and apoptosis. These results suggest that apoptosis inhibition associated with proliferation block could depend on modulation of the TRAIL apoptotic pathway and regulation of the Mcl-1 protein level. In summary, we demonstrate that the balance of processes leading to regulation of proliferation and differentiation of myeloid cells can modulate cell sensitivity to apoptosis-inducing stimuli.

* Zobrazit nápovědu

Upřesnit dle MeSH