Regulation of cell death in human fetal and adult ovaries—Role of Bok and Bcl-XL

Jääskeläinen, Minna; Nieminen, Anni I.; Pökkylä, Reeta-Maria; Kauppinen, Marjut; Liakka, Annikki; Heikinheimo, Markku; Vaskivuo, Tommi; Klefström, Juha; Tapanainen, Juha S.

doi:10.1016/j.mce.2010.07.020

Cited by 25 publications

(16 citation statements)

References 38 publications

(45 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Western blot assay was used in this study to detect specific proteins in the homogenized extracted colon. These proteins play essential roles in the development of new cancer drugs [54]. Bcl-2 plays a vital role in controlling the process of cell death by blocking various apoptosis signals.…”

Section: Discussionmentioning

confidence: 99%

Chemopreventive Evaluation of a Schiff Base Derived Copper (II) Complex against Azoxymethane-Induced Colorectal Cancer in Rats

et al. 2014

View full text Add to dashboard Cite

BackgroundBased on the potential of Schiff base compounds to act as sources for the development of cancer chemotherapeutic agents, this in vivo study was performed to investigate the inhibitory properties of the synthetic Schiff base compound Cu(BrHAP)2 on colonic aberrant crypt foci (ACF).MethodologyThis study involved five groups of male rats. The negative control group was injected with normal saline once a week for 2 weeks and fed 10% Tween 20 for 10 weeks, the cancer control group was subcutaneously injected with 15 mg/kg azoxymethane once per week for two consecutive weeks, the positive control group was injected with 15 mg/kg azoxymethane once per week for two consecutive weeks and 35 mg/kg 5-fluorouracil (injected intra-peritoneally) for 4 weeks, and the experimental groups were first injected with 15 mg/kg azoxymethane once per week for two consecutive weeks and then fed 2.5 or 5 mg/kg of the Schiff base compound once a day for 10 weeks. Application of the Schiff base compound suppressed total colonic ACF formation by up to 72% to 74% (P<0.05) when compared with the cancer control group. Analysis of colorectal specimens revealed that treatments with the Schiff base compound decreased the mean crypt scores in azoxymethane-treated rats. Significant elevations of superoxide dismutase, glutathione peroxidase and catalase activities and a reduction in the level of malondialdehyde were also observed. Histologically, all treatment groups exhibited significant decreases in dysplasia compared to the cancer control group (P<0.05). Immunohistochemical staining demonstrated down-regulation of the PCNA protein. Comparative western blot analysis revealed that COX-2 and Bcl2 were up-regulated and Bax was down-regulated compared with the AOM control group.ConclusionThe current study demonstrated that the Cu(BrHAP)2 compound has promising chemoprotective activities that are evidenced by significant decreases in the numbers of ACFs in azoxymethane-induced colon cancer.

show abstract

Section: Discussionmentioning

confidence: 99%

Chemopreventive Evaluation of a Schiff Base Derived Copper (II) Complex against Azoxymethane-Induced Colorectal Cancer in Rats

et al. 2014

View full text Add to dashboard Cite

show abstract

“…BCL2L1 (bcl-xl) encodes a protein belonging to the BCL-2 protein family, whose protein members act as anti- or pro-apoptotic regulators [33]. Over-expression of the Bcl-xL protein is known to confer resistance to a broad range of potentially apoptotic stimuli in carcinogenesis processes including oncogene activation, hypoxia and matrix detachment [34]–[37].…”

Section: Discussionmentioning

confidence: 99%

Global Analysis of DNA Methylation by Methyl-Capture Sequencing Reveals Epigenetic Control of Cisplatin Resistance in Ovarian Cancer Cell

Jin

Lou

et al. 2011

PLoS ONE

View full text Add to dashboard Cite

Cisplatin resistance is one of the major reasons leading to the high death rate of ovarian cancer. Methyl-Capture sequencing (MethylCap-seq), which combines precipitation of methylated DNA by recombinant methyl-CpG binding domain of MBD2 protein with NGS, global and unbiased analysis of global DNA methylation patterns. We applied MethylCap-seq to analyze genome-wide DNA methylation profile of cisplatin sensitive ovarian cancer cell line A2780 and its isogenic derivative resistant line A2780CP. We obtained 21,763,035 raw reads for the drug resistant cell line A2780CP and 18,821,061reads for the sensitive cell line A2780. We identified 1224 hyper-methylated and 1216 hypomethylated DMRs (differentially methylated region) in A2780CP compared to A2780. Our MethylCap-seq data on this ovarian cancer cisplatin resistant model provided a good resource for the research community. We also found that A2780CP, compared to A2780, has lower observed to expected methylated CpG ratios, suggesting a lower global CpG methylation in A2780CP cells. Methylation specific PCR and bisulfite sequencing confirmed hypermethylation of PTK6, PRKCE and BCL2L1 in A2780 compared with A2780CP. Furthermore, treatment with the demethylation reagent 5-aza-dC in A2780 cells demethylated the promoters and restored the expression of PTK6, PRKCE and BCL2L1.

show abstract

“…Much attention has focused on apoptosis (Vaskivuo et al 2001, Fulton et al 2005, Poljicanin et al 2012, although emerging evidence also suggests that the mode of germ cell elimination, especially in meiosis, may be ovary specific and occurs by several mechanisms not limited to the classical apoptotic pathways (Abir et al 2002). Efforts to identify and quantitate the characteristics of apoptosis as a principal or coherent explanation for oocyte depletion in the human fetal ovary often demonstrate the difficulties and inconsistencies in interpretation of cause and effect, probably due to differential gene expression among cell populations that may be at rest, proliferating, maturing, dying, or phagocytosing (Kurilo 1981, De Pol et al 1997, Vaskivuo et al 2001, Abir et al 2002, Fulton et al 2005, Stoop et al 2005, Albamonte et al 2008, Jaaskelainen et al 2010, Boumela et al 2011, Poljicanin et al 2012. Nevertheless, these and other studies demonstrate that the Bcl2 gene family is an important regulator (among other factors) of the balance between survival or death of oocytes prior to primordial follicle formation.…”

Section: Establishing the Primordial Follicle Reservementioning

confidence: 99%

The dynamics of the primordial follicle reserve

Kerr¹,

Myers²,

Anderson³

2013

Reproduction

128

View full text Add to dashboard Cite

The female germline comprises a reserve population of primordial (non-growing) follicles containing diplotene oocytes arrested in the first meiotic prophase. By convention, the reserve is established when all individual oocytes are enclosed by granulosa cells. This commonly occurs prior to or around birth, according to species. Histologically, the 'reserve' is the number of primordial follicles in the ovary at any given age and is ultimately depleted by degeneration and progression through folliculogenesis until exhausted. How and when the reserve reaches its peak number of follicles is determined by ovarian morphogenesis and germ cell dynamics involving i) oogonial proliferation and entry into meiosis producing an oversupply of oocytes and ii) large-scale germ cell death resulting in markedly reduced numbers surviving as the primordial follicle reserve. Our understanding of the processes maintaining the reserve comes primarily from genetically engineered mouse models, experimental activation or destruction of oocytes, and quantitative histological analysis. As the source of ovulated oocytes in postnatal life, the primordial follicle reserve requires regulation of i) its survival or maintenance, ii) suppression of development (dormancy), and iii) activation for growth and entry into folliculogenesis. The mechanisms influencing these alternate and complex inter-related phenomena remain to be fully elucidated. Drawing upon direct and indirect evidence, we discuss the controversial concept of postnatal oogenesis. This posits a rare population of oogonial stem cells that contribute new oocytes to partially compensate for the age-related decline in the primordial follicle reserve.Reproduction (2013) 146 R205-R215

show abstract

Regulation of cell death in human fetal and adult ovaries—Role of Bok and Bcl-XL

Cited by 25 publications

References 38 publications

Chemopreventive Evaluation of a Schiff Base Derived Copper (II) Complex against Azoxymethane-Induced Colorectal Cancer in Rats

Chemopreventive Evaluation of a Schiff Base Derived Copper (II) Complex against Azoxymethane-Induced Colorectal Cancer in Rats

Global Analysis of DNA Methylation by Methyl-Capture Sequencing Reveals Epigenetic Control of Cisplatin Resistance in Ovarian Cancer Cell

The dynamics of the primordial follicle reserve

Contact Info

Product

Resources

About