Changes in expression of anti-apoptotic protein, cflip, in granulosa cells during follicular atresia in porcine ovaries

Matsuda‐Minehata, Fuko; Goto, Yasufumi; Inoue, N.; Manabe, Noboru

doi:10.1002/mrd.20349

Cited by 34 publications

(52 citation statements)

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“…Overexpression of pFADD and pprocaspase-8 induced cell death in the HeLa-K cells. To date, we have investigated the follicular atretic mechanisms of follicular atresia in porcine ovaries [18][19][20][21][22][26][27][28][29][30][31] and have shown that g r a n u l o s a c e l l a p o p t o s i s i s a d o m i n a n t phenomenon in follicular atresia. Therefore, we examined whether overexpressed pFADD and pprocaspase-8 can induce apoptosis in the granulosa cells of human, murine, and porcine origin (KGN, KK1 and JC410, respectively).…”

Section: Apoptosis Inductivitymentioning

confidence: 99%

“…We previously reported that death ligand/ receptor systems act as initiators of apoptosis in porcine granulosa cells [22,30,31] and showed that an intracellular inhibitory protein, cFLIP, inhibits apoptosis in granulosa cells by binding with the D E D o f F A D D a n d / o r p r o c a s p a s e -8 a n d interrupting the recruitment of procaspase-8 to FADD [29,30]. In the present study, we showed that both the molecular construction and function of apoptotic signaling factors are highly conserved.…”

Section: Apoptosis Inductivitymentioning

confidence: 99%

“…Then, the apoptotic signal is transduced as described above. Recently, we found that cellular FLICE-like inhibitory protein (cFLIP) plays an anti-apoptotic role in the granulosa cells of healthy follicles in porcine ovaries [28][29][30][31]. Two splicing variants, a short form (cFLIP S ) and a long form (cFLIP L ), were identified.…”

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confidence: 99%

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Molecular Characteristics of Porcine Fas-associated Death Domain (FADD) and Procaspase-8

Inoue

Matsuda‐Minehata

Goto

et al. 2007

Journal of Reproduction and Development

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Abstract. To reveal the intracellular signal transduction molecules involved in granulosa cell apoptosis in porcine ovarian follicles, we cloned the porcine Fas-associated death domain (FADD), an adaptor protein for the cell death receptor, and procaspase-8, an initiator caspase. Porcine FADD (pFADD) was 636 bp (211 amino acids: aa) long and showed 74.0 and 65.4% homology with human and murine FADD, respectively. Porcine procaspase-8 (pprocaspase-8) was 1,431 bp (476 aa) long and 70.6 and 63.4% homologous with human and murine procaspase-8, respectively. To confirm the apoptosis-inducing abilities, we constructed pFADD and pprocaspase-8 cDNA expression vectors with enhanced green fluorescence protein (EGFP) and then transfected them into human uterine cervix tumor (HeLa-K), human granulosa cell-derived (KGN), murine granulosa-derived tumor (KK1), and porcine granulosa cell-derived (JC410) cells. When pFADD and pprocaspase-8 were overexpressed, cell death was induced in these transfected cells. However when caspase-inhibitor p35 was cotransfected, cell death was inhibited. The pFADD and pprocaspase-8 genes are well conserved, as are the physiological functions of their products. Key words: Apoptosis, Caspase-8, Fas-associated death domain (FADD), Granulosa cell, Porcine ovary (J. Reprod. Dev. 53: [427][428][429][430][431][432][433][434][435][436] 2007) poptosis is an important phenomenon involved i n c e l l s u r v i v a l a n d / o r d e a t h d u r i n g differentiation and development [1,2]. The death ligand and receptor systems are considered to be apoptosis-inducing factors [3][4][5][6][7]. Death receptors, which belong to the tumor necrosis factor (TNF) receptor family, are membrane-binding proteins with a death domain (DD) in their intracellular regions. An adaptor protein, such as Fasassociating death domain protein (FADD), which has a DD in the C-terminal region and a death effector domain (DED) in the N-terminal region, is recruited when each specific ligand binds to its r e c e p t o r [ 8 -1 0 ] . T h e n , F A D D b i n d s w i t h procaspase-8 (also called FLICE), which has two DEDs in the N-teminal region [11,12]. These molecules compose the death-inducing signaling complex (DISC). As a result of the proteolytic autoactivation of procaspase-8 [13], subunit protein 18 (p18) and 11 (p11) are released into the cytoplasm and reform a proteolytic component that c l e a v e s m a n y s u b s t r a t e p r o t e i n s , s u c h a s

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Section: Apoptosis Inductivitymentioning

confidence: 99%

Section: Apoptosis Inductivitymentioning

confidence: 99%

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Molecular Characteristics of Porcine Fas-associated Death Domain (FADD) and Procaspase-8

Inoue

Matsuda‐Minehata

Goto

et al. 2007

Journal of Reproduction and Development

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“…Immunohistochemical analyses demonstrated that the cFLIP protein is highly expressed in the granulosa cells of healthy follicles but weakly expressed in those of the atretic follicles (Matsuda-Minehata et al, 2005). Luteal tissue formation is characterized by the differentiation and proliferation of cells derived from granulosa, theca, and vascular endothelium in the post-ovulatory follicle (Jablonka-Shariff et al, 1993;Murphy, 2000).…”

Section: Introductionmentioning

confidence: 99%

Expression and localization of cFLIP anti-apoptotic protein in the porcine corpus luteum and corpora albicans during the estrous cycle and pregnancy

Hz¹,

Ws²,

Tian³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. We determined expression and localization of the antiapoptotic cellular FLICE inhibitory protein (cFLIP) in the porcine corpora lutea (CL) and corpus albicans (CA) during estrous and pregnancy. The CL and CA were collected at different stages of estrous to determine cFLIP immunolocalization, and mRNA and protein expression. The mRNA expression of the short cFLIP isoform (cFLIP S ) was higher at the early and mid CL stages, and lower by the late CL stage (P < 0.01); mRNA expression of the long cFLIP isoform (cFLIP L ) was higher at the mid CL stage, and lower at the early and late CL stages (P < 0.01). Levels of cFLIP S and cFLIP L were steady and high during the early and mid CL stages, and had significantly decreased (P < 0.01) by the late stage. The cFLIP protein was highly expressed in the early and mid CL stages of estrous, but weakly expressed in the late stage. Expression of cFLIP S showed no significant difference between preovulatory corpus albicans (CA1) and corpus (2015) albicans (CA2) coexistent with the CL from the previous estrus, but cFLIP L mRNA expression was higher during CA1 than CA2. The expression of cFLIP S showed no significant difference between CA1 and CA2, but cFLIP L was not detected. The cFLIP protein was weakly expressed in the CA. Expression of cFLIP S and cFLIP L mRNA and proteins was observed in the CL, and the cFLIP protein was highly expressed during pregnancy. We propose that cFLIP S/L acts as a survival factor, and performs an anti-apoptotic function in the porcine CL.

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“…The researches in this subject showed that granulosa cells of healthy follicles had highly expressed cFLIP L mRNA and proteins, whereas the atretic ones had decreased levels (Goto et al, 2004). The mRNA levels of cFLIP S in granulosa cells are low and showed no changes among the stages of follicular development (Matsuda-Minehata et al, 2005. cFLIP acts as a survival promoting factor in granulosa cells and not only inhibits Fas-signalling, but also can inhibit TNF α and TRAIL signalling (Manabe et al, 2008;Cheng et al, 2007;Manabe et al, 2003).…”

Section: Antiapoptotic Regulators In the Cellmentioning

confidence: 95%

Role of apoptosis-related factors in follicular atresia

Gumus¹,

Kılıç²,

Zülfikaroğlu³

2013

Int. J. Genet. Mol. Biol.

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Follicular atresia is the term used for the fate of follicles which undergo degenerative changes before rupturing during ovulation. Recent studies suggest that granulosa cell apoptosis play a major role in follicular atresia. The factors which lead the cell to apoptosis and which protect the cell death, still remain complicated and more studies are needed to elucidate the whole process. Here in this review, we aimed to simplify the factors and mechanisms taking place in granulosa cell apoptosis, to make the process more understandable.Key words: Granulosa cell, apoptosis, follicular atresia. INTRODUCTİONWhen a female human embryo is 8-week-old, she has 600,000 germ cells in her gonads and this number increases to 6 to 7 million at 20 weeks of gestation. But with the increasing rate of atresia, the number declines progressively and 1 million oocytes are present in the newborn, whereas 300,000 oocytes remain in puberty, of which approximately 400 will ovulate during the fertile lifespan (Oktem and Oktay, 2008;Gougeon, 1996;Matova and Cooley, 2001).'Follicular atresia' term is used to define antral follicles undergoing degenerative changes before rupturing during ovulation. It is initiated within the granulosa cell layer and subsequently in the theca cells Hsueh et al., 1994). In mammals, the basic mechanism of follicular atresia is apoptosis (Depalo et al., 2003). Apoptosis is a way which multicellular organisms use to eliminate unwanted cells in response to developmental signals or toxic stimuli (Quirck et al., 2004). It is regulated at the level of transcription or translation (Manabe et al., 2008). Major morphological characteristics of apoptosis are the internucleosomal DNA fragmentation, cell shrinkage, plasma membrane blebbing, and the apoptotic body formation (Schwartzman and Cidlowski, 1993).Granulosa cells possess endogenous pathways to trigger apoptosis, that are inhibited in the presence of survi-*Corresponding author. E-mail: zebru33@gmail.com. Tel: +90 (312) 2158652. Fax: +90 (312) 3124931.val factors (Quirck et al., 2004). To date, many apoptosisrelated factors have been implicated in follicular atresia, including death ligands and receptors, Bcl-2 family proteins, Nodal, caspases, growth factors, gonadotropins, and calcium. In this report, we will overview these factors one by one. Proapoptotic regulators in the cell death receptorligand systemDeath receptors constitute a subgroup within the tumor necrosis factor (TNF) receptor family. They are located on the cell surface, anchored to the cell membrane, are trimerized and have cytoplasmic death domains (DDs) which are necessary to induce apoptosis (Park et al., 2005;Ashkenazi and Dixit, 1998;Wallach et al., 1999). Fas receptor, TNF receptor, and TNF related apoptosis inducing ligand receptors (TRAILr) are the members of TNF receptor family that are found to have roles in follicular atresia in mammalian ovaries (Park et al., 2005).In most of the cases, the cell death receptor-mediated apoptosis takes place as follows:1) The cell death ligand binds to...

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Changes in expression of anti-apoptotic protein, cflip, in granulosa cells during follicular atresia in porcine ovaries

Cited by 34 publications

References 28 publications

Molecular Characteristics of Porcine Fas-associated Death Domain (FADD) and Procaspase-8

Molecular Characteristics of Porcine Fas-associated Death Domain (FADD) and Procaspase-8

Expression and localization of cFLIP anti-apoptotic protein in the porcine corpus luteum and corpora albicans during the estrous cycle and pregnancy

Role of apoptosis-related factors in follicular atresia

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