Overexpression of RGPR-p117 suppresses apoptotic cell death and its related gene expression in cloned normal rat kidney proximal tubular epithelial NRK52E cells

Abstract The overexpression of hepatocyte nuclear factor-1 beta (HNF1β) in endometriotic lesion has been demonstrated. However, the role of HNF1β in endometriosis remains largely unknown. Human endometriotic 12Z cells showed higher level of HNF1β when compared with normal endometrial HES cells. In human endometriotic 12Z cells, HNF1β knockdown increased susceptibility to apoptotic cell death by oxidative stress, while HNF1β overexpression suppressed apoptosis. In addition, HNF1β knockdown and overexpression significantly decreased and increased, respectively, the expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)-dependent antiapoptotic genes. Knockdown of the antiapoptotic genes significantly reduced the HNF1β-induced resistance against oxidative stress in 12Z cells. Furthermore, HNF1β regulated the transcriptional activity of NF-κB, and an NF-κB inhibitor suppressed the HNF1β-enhanced NF-κB-dependent antiapoptotic gene expression and the resistance of the 12Z cells against cell death. Taken together, these data suggest that HNF1β overexpression may protect endometriotic cells against oxidative damage by augmenting antiapoptotic gene expression.

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Overexpression of PU.1 Induces Growth and Differentiation Inhibition and Apoptotic Cell Death in Murine Erythroleukemia Cells

Blood ◽

10.1182/blood.v89.4.1383 ◽

1997 ◽

Vol 89 (4) ◽

pp. 1383-1393 ◽

Cited By ~ 72

Author(s):

Toshiyuki Yamada ◽

Nobuo Kondoh ◽

Mana Matsumoto ◽

Midori Yoshida ◽

Akihiko Maekawa ◽

...

Keyword(s):

Gene Expression ◽

Cell Death ◽

Growth Inhibition ◽

Apoptotic Cell ◽

Globin Gene ◽

Apoptotic Cell Death ◽

Activation Domain ◽

Ets Domain ◽

Murine Erythroleukemia ◽

Globin Gene Expression

Abstract PU.1 is a member of the ets family of transcription factors and is expressed in Friend virus-induced murine erythroleukemia (MEL) cells as a consequence of proviral integration into the PU.1/Spi-1 locus. After induction of MEL cell differentiation by treatment with dimethylsulfoxide (DMSO), expression of the PU.1/Spi-1 gene decreased before induction of β-globin gene expression. Overexpression of PU.1 by using a zinc-inducible expression plasmid in MEL cells resulted in unexpected growth inhibition of the transfectants. When PU.1-overexpressing transfectants were treated with DMSO, growth inhibition became much pronounced and apoptosis was induced. Expression of the β-globin gene was not induced under this condition. Neither growth inhibition nor apoptosis was induced in MEL cells after expression of mutant PU.1 proteins with a deletion of the activation domain or the DNA-binding Ets domain irrespective of the presence of DMSO. Interestingly, β-globin gene expression was not induced in the transfectants expressing the former mutant, whereas it was induced in those expressing the latter one in the presence of DMSO. These results indicate that overexpression of PU.1 in MEL cells results in growth and differentiation inhibition and, in conjunction with DMSO treatment, apoptotic cell death. These results also suggest that the activation domain and the Ets domain of PU.1 contribute differently to induction of these effects.

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