Long-term 17α-ethinyl estradiol treatment decreases cyclin E and cdk2 expression, reduces cdk2 kinase activity and inhibits S phase entry in regenerating rat liver

Koroxenidou, Lena; Ohlson, Lena C. E.; Hällström, Inger Porsch

doi:10.1016/j.jhep.2005.02.050

Cited by 8 publications

(6 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These delayed transits allow cells to repair DNA damage before replication or segregation of defective chromosomes and propagation of heritable genetic errors (Liu and Martin-Kulesz 2001). Koroxenidou et al (2005) reported that long-term EE 2 treatment decrease cyclin E and Cdk2 expression, reduces Cdk2 kinase activity and inhibits S phase cell entry in regenerating rat liver, suggesting a block in late G1 or G1/S transition. Furthermore, an increase in p53 and p21 expression levels was observed, indicating a possible role for the p53/p21 pathway in the cell cycle block.…”

Section: Discussionmentioning

confidence: 99%

Zebrafish (Danio rerio) life-cycle exposure to chronic low doses of ethinylestradiol modulates p53 gene transcription within the gonads, but not NER pathways

et al. 2012

View full text Add to dashboard Cite

Parental full life-cycle exposure to ethinylestradiol (EE₂) significantly affects embryo development and survival. One of the possible mechanisms of action of EE₂ may involve the impairment of an organism's ability to repair DNA damage. DNA repair mechanisms have sophistically evolved to overcome DNA damaging hazards that threaten the integrity of the genome. In the present study, changes in the transcription levels of key genes involved in two of the most thoroughly studied DNA repair systems in mammals were evaluated in adult zebrafish (Danio rerio) gonad upon full life-cycle exposure to chronic environmentally low levels of EE₂ (i.e., 0.5, 1 and 2 ng/L EE₂). Real time PCR was used to analyse the expression levels of nucleotide excision repair genes (NER) as well as the tumor suppressor p53 and downstream selected effectors, i.e., p21 (cyclin-dependent kinase inhibitor), GADD45α (growth arrest and DNA damage induced 45, alpha), bax (bcl2-associated X protein) and p53 key regulator MDM2 (murine double minute 2 protein). NER genes transcription levels in gonads did not differ significantly among treatments. In contrast, the number of transcripts of p53 gene was significantly increased in male gonads at all EE₂ exposure concentrations and in females at 1 ng/L EE₂. Despite the increase in p53 transcripts, transcription levels of p21, GADD45α and bax genes were not affected upon EE₂ treatment, whereas MDM2 gene expression significantly increased in females at the intermediate EE₂ dose (1 ng/L). Overall, the present study indicate that chronic low levels of EE₂ significantly modulates the transcription of p53, a key gene involved in DNA repair, particularly in male zebrafish gonads, which supports the hypothesis of an impact of EE2 in male gonad DNA repair pathways.

show abstract

Section: Discussionmentioning

confidence: 99%

Zebrafish (Danio rerio) life-cycle exposure to chronic low doses of ethinylestradiol modulates p53 gene transcription within the gonads, but not NER pathways

et al. 2012

View full text Add to dashboard Cite

show abstract

“…Cyclin E contributes to the proliferation of normal cells by accelerating the G1-S phase turnover. Cdk2 activated by cyclin A and cyclin E controls the G1-S phase by phosphorylation of pRB [11][12][13][14]. The decrease in expressions of these proteins as well as PCNA (a marker of S-phase of mitosis) indicated that HG and GI inhibit cell proliferation by blocking S-phase differentiation.…”

Section: Discussionmentioning

confidence: 99%

Effects of high glucose plus high insulin on proliferation and apoptosis of mouse endothelial progenitor cells

et al. 2008

View full text Add to dashboard Cite

show abstract

“…These kinase systems phosphorylate various substrates, including the product of the retinoblastoma susceptibility gene (pRB), in order to initiate DNA synthesis [Gad et al, 2004;White et al, 2005]. Cyclin D1-CDK4 and cyclin E-CDK2 play a key role in cell cycle progression from G1 to S phase in most cell types, including hepatocytes [Alisi et al, 2003;Koroxenidou et al, 2005]. Along with the increases in cyclins/CDKs, L-leucine treatment mediated a concomitant decrease in p21 WAF1/Cip1 expression.…”

Section: à7mentioning

confidence: 99%

L‐leucine increases [³H]‐thymidine incorporation in chicken hepatocytes: Involvement of the PKC, PI3K/Akt, ERK1/2, and mTOR signaling pathways

Lee

et al. 2008

J of Cellular Biochemistry

View full text Add to dashboard Cite

This study examined how L-leucine affected DNA synthesis and cell cycle regulatory protein expression in cultured primary chicken hepatocytes. L-Leucine promoted DNA synthesis in a dose- and time-dependent manner, with concomitant increases in cyclin D1 and cyclin E expression. Phospholipase C (PLC) and protein kinase C (PKC) mediated the L-leucine-induced increases in [3H]-thymidine incorporation and cyclin D1/CDK4 and cyclin E/CDK2 expression, as U73122 (a PLC inhibitor) or bisindolylmaleimide I (a PKC blocker) inhibited these effects. L-Leucine also increased PKC phosphorylation and intracellular Ca2+ levels. L-Leucine-mediated increases in [3H]-thymidine incorporation and cyclin/CDK expression were sensitive to LY 294002 (PI3K inhibitor), Akt inhibitor, PD 98059 (MEK inhibitor). It was also observed that L-leucine-induced increases of cyclin/CDK expression were inhibited by PI3K siRNA and ERK siRNA; L-leucine increased extracellular signal-regulated kinases 1/2 (ERK1/2) and Akt phosphorylation levels. Bisindolylmaleimide I attenuated L-leucine-induced phosphorylation of ERK1/2 but did not influence Akt phosphorylation, and PI3K siRNA and LY 294002 inhibited L-leucine-induced ERK1/2 phosphorylation, suggesting some cross-talk between the PKC and ERK1/2 or PI3K/Akt and ERK1/2 pathways. L-Leucine also increased the levels of phosphorylated molecular target of rapamycin (mTOR) and two of its targets, ribosomal protein S6 kinase (p70S6K), and 4E binding protein 1 (4E-BP1); furthermore, rapamycin (an mTOR inhibitor) blocked all of the mitogenic effects of L-leucine. In addition, Akt inhibitor blocked L-leucine-induced mTOR phosphorylation. In conclusion, L-leucine stimulated DNA synthesis and promoted cell cycle progression in primary cultured chicken hepatocytes through PKC, ERK1/2, PI3K/Akt, and mTOR.

show abstract

Long-term 17α-ethinyl estradiol treatment decreases cyclin E and cdk2 expression, reduces cdk2 kinase activity and inhibits S phase entry in regenerating rat liver

Cited by 8 publications

References 52 publications

Zebrafish (Danio rerio) life-cycle exposure to chronic low doses of ethinylestradiol modulates p53 gene transcription within the gonads, but not NER pathways

Zebrafish (Danio rerio) life-cycle exposure to chronic low doses of ethinylestradiol modulates p53 gene transcription within the gonads, but not NER pathways

Effects of high glucose plus high insulin on proliferation and apoptosis of mouse endothelial progenitor cells

L‐leucine increases [³H]‐thymidine incorporation in chicken hepatocytes: Involvement of the PKC, PI3K/Akt, ERK1/2, and mTOR signaling pathways

Contact Info

Product

Resources

About

Long-term 17α-ethinyl estradiol treatment decreases cyclin E and cdk2 expression, reduces cdk2 kinase activity and inhibits S phase entry in regenerating rat liver

Cited by 8 publications

References 52 publications

Zebrafish (Danio rerio) life-cycle exposure to chronic low doses of ethinylestradiol modulates p53 gene transcription within the gonads, but not NER pathways

Zebrafish (Danio rerio) life-cycle exposure to chronic low doses of ethinylestradiol modulates p53 gene transcription within the gonads, but not NER pathways

Effects of high glucose plus high insulin on proliferation and apoptosis of mouse endothelial progenitor cells

L‐leucine increases [3H]‐thymidine incorporation in chicken hepatocytes: Involvement of the PKC, PI3K/Akt, ERK1/2, and mTOR signaling pathways

Contact Info

Product

Resources

About

L‐leucine increases [³H]‐thymidine incorporation in chicken hepatocytes: Involvement of the PKC, PI3K/Akt, ERK1/2, and mTOR signaling pathways