Cortisol Is a Suppressor of Apoptosis in Bovine Corpus Luteum1

Komiyama, Junichi; Nishimura, Ryo; Lee, Hwa Yong; Sakumoto, Ryosuke; Tetsuka, Masafumi; Acosta, Tomás J.; Skarzynski, Dariusz J.; Okuda, Kiyoshi

doi:10.1095/biolreprod.107.065656

Cited by 49 publications

(17 citation statements)

References 58 publications

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“…27,28 The selected stress response genes are present and highly conserved in most cell types of metazoans and are activated at significantly lower toxicant concentrations than those causing overt cellular injury, 29,30 which make them suitable to reveal potential toxicity mechanisms comprehensively. Specific toxicity and stress response-based studies have been used by both our group 28,31 and others, with specific focus on oxidative damage, 32,33 DNA damage, 34 and inflammation and apoptosis, 35,36 to provide important insights into the toxicological potential elicited by chemicals. These in vitro high throughput molecular assays provide fast yet informative results for initial toxicity screening and risk identification to guide further extensive toxicity evaluation, as needed for the case of the 4-MCHM chemical spill.…”

Section: ■ Introductionmentioning

confidence: 99%

Toxicity Assessment of 4-Methyl-1-cyclohexanemethanol and Its Metabolites in Response to a Recent Chemical Spill in West Virginia, USA

Lan

Gao

et al. 2015

Environ. Sci. Technol.

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The large-scale chemical spill on January 9, 2014 from coal processing and cleaning storage tanks of Freedom Industries in Charleston affected the drinking water supply to 300,000 people in Charleston, West Virginia metropolitan, while the short-term and long-term health impacts remain largely unknown and need to be assessed and monitored. There is a lack of publically available toxicological information for the main contaminant 4-methyl-1-cyclohexanemethanol (4-MCHM). Particularly, little is known about 4-MCHM metabolites and their toxicity. This study reports timely and original results of the mechanistic toxicity assessment of 4-MCHM and its metabolites via a newly developed quantitative toxicogenomics approach, employing proteomics analysis in yeast cells and transcriptional analysis in human cells. These results suggested that, although 4-MCHM is considered only moderately toxic based on the previous limited acute toxicity evaluation, 4-MCHM metabolites were likely more toxic than 4-MCHM in both yeast and human cells, with different toxicity profiles and potential mechanisms. In the yeast library, 4-MCHM mainly induced chemical stress related to transmembrane transport and transporter activity, while 4-MCHM metabolites of S9 mainly induced oxidative stress related to antioxidant activity and oxidoreductase activity. With human A549 cells, 4-MCHM mainly induced DNA damage-related biomarkers, which indicates that 4-MCHM is related to genotoxicity due to its DNA damage effect on human cells and therefore warrants further chronic carcinogenesis evaluation.

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Section: ■ Introductionmentioning

confidence: 99%

Toxicity Assessment of 4-Methyl-1-cyclohexanemethanol and Its Metabolites in Response to a Recent Chemical Spill in West Virginia, USA

Lan

Gao

et al. 2015

Environ. Sci. Technol.

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“…Apoptosis of luteal cells and CL vascular regression are regulated/modulated by pro-inflammatory cytokines, i.e., tumor necrosis factor-α (TNF), interferon-γ (IFNG), FAS ligand (FASL) and nitric oxide (NO)678910. On the other hand, P4, cortisol and luteotropic PGs (PGE2 and PGI2) protect LSCs against apoptosis111213. As mentioned above, apoptosis in CL is regulated by complex mechanisms inducing a cascade of several immune-endocrine factors and mediators.…”

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confidence: 99%

“…During the past several decades, apoptosis is considered to be the most studied local mechanism regulating structural luteolysis of the bovine CL. Thus, a great number of studies have been focused on type-I programmed cell death of steroidogenic and accessory luteal cells678910111213. However, luteolysis, especially exogenous PGF-induced luteolysis, is a very rapid process and the bovine CL completely disappears from the ovary within 2 days after PGF injection.…”

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confidence: 99%

Programmed necrosis - a new mechanism of steroidogenic luteal cell death and elimination during luteolysis in cows

Hojo

Siemieniuch

Łukasik

et al. 2016

Sci Rep

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Programmed necrosis (necroptosis) is an alternative form of programmed cell death that is regulated by receptor-interacting protein kinase (RIPK) 1 and 3-dependent, but is a caspase (CASP)-independent pathway. In the present study, to determine if necroptosis participates in bovine structural luteolysis, we investigated RIPK1 and RIPK3 expression throughout the estrous cycle, during prostaglandin F2α (PGF)-induced luteolysis in the bovine corpus luteum (CL), and in cultured luteal steroidogenic cells (LSCs) after treatment with selected luteolytic factors. In addition, effects of a RIPK1 inhibitor (necrostatin-1, Nec-1; 50 μM) on cell viability, progesterone secretion, apoptosis related factors and RIPKs expression, were evaluated. Expression of RIPK1 and RIPK3 increased in the CL tissue during both spontaneous and PGF-induced luteolysis (P < 0.05). In cultured LSCs, tumor necrosis factor α (TNF; 2.3 nM) in combination with interferon γ (IFNG; 2.5 nM) up-regulated RIPK1 mRNA and protein expression (P < 0.05). TNF + IFNG also up-regulated RIPK3 mRNA expression (P < 0.05), but not RIPK3 protein. Although Nec-1 prevented TNF + IFNG-induced cell death (P < 0.05), it did not affect CASP3 and CASP8 expression. Nec-1 decreased both RIPK1 and RIPK3 protein expression (P < 0.05). These findings suggest that RIPKs-dependent necroptosis is a potent mechanism responsible for bovine structural luteolysis induced by pro-inflammatory cytokines.

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“…The presence of these HSD11Bs in the ovary has been reported in various species such as humans (Michael et al 1993, Albiston et al 1994, Michael et al 1997, Tetsuka et al 1997, Ricketts et al 1998, Smith et al 2000, Rae et al 2004, macaques (Fru et al 2006), cattle (Tetsuka et al 2003, Komiyama et al 2008, Tetsuka et al 2010, Amweg et al 2013, pigs (Sunak et al 2007, Webb et al 2008 and rats (Benediktsson et al 1992, Tetsuka et al 1999b, Gomez-Sanchez et al 2009.…”

Section: Discussionmentioning

confidence: 92%

“…Various ovarian cells have been shown to express HSD11Bs, such as granulosa cells (Tetsuka et al 1997, Ricketts et al 1998, Tetsuka et al 1999b, luteinized granulosa cells (Michael et al 1997, Tetsuka et al 1997, luteal cells (Ricketts et al 1998, Komiyama et al 2008, thecal or thecal interstitial cells (Tetsuka et al 1999b, Tetsuka et al 2010) and ovarian surface epithelial cells (Rae et al 2004). The presence of HSD11Bs in the oocyte or COC has been demonstrated by various methods, but the results are not consistent among the observations.…”

Section: Discussionmentioning

confidence: 99%

Glucocorticoid metabolism in the bovine cumulus–oocyte complex matured in vitro

et al. 2016

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Glucocorticoid action in target organs is regulated by relative activities of 11b-HSD type 1 (HSD11B1) that mainly converts cortisone to active cortisol and type 2 (HSD11B2) that inactivates cortisol to cortisone. HSD11Bs have been shown to be expressed in the ovary of various species. However, little is known about the expression and activity of HSD11Bs in the bovine cumulus-oocyte complex (COC). In the present study, we investigated the expression and activities of HSD11Bs in in vitro-matured (IVM) bovine COCs. Bovine COCs were matured in M199 supplemented with or without FSH and FCS. The expression of HSD11B1 and HSD11B2 was measured by using quantitative RT-PCR in denuded oocytes (DO) and cumulus cells (CC). Reductive and oxidative activities of HSD11Bs were determined by radiometric conversion assay using labeled cortisol, cortisone or dexamethasone in intact COCs, DO or CC in the presence or absence of 11-keto-progesterone (11kP), a selective inhibitor of HSD11B2. The presence of HSD11Bs in the oocyte was examined by immunofluorescence microscopy. Oocytes exclusively expressed HSD11B2 and its expression and activity were largely unchanged during IVM. CC, on the other hand, exclusively expressed HSD11B1 and its expression and activity were upregulated as IVM progressed. As a result, the net glucocorticoid metabolism shifted from inactivation to activation towards the end of IVM. These results indicate that the bovine COC is capable of modulating local glucocorticoid concentration and, by doing so, may create an environment that is favorable to ovulating oocyte for maturation, fertilization and subsequent development.

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Cortisol Is a Suppressor of Apoptosis in Bovine Corpus Luteum1

Cited by 49 publications

References 58 publications

Toxicity Assessment of 4-Methyl-1-cyclohexanemethanol and Its Metabolites in Response to a Recent Chemical Spill in West Virginia, USA

Toxicity Assessment of 4-Methyl-1-cyclohexanemethanol and Its Metabolites in Response to a Recent Chemical Spill in West Virginia, USA

Programmed necrosis - a new mechanism of steroidogenic luteal cell death and elimination during luteolysis in cows

Glucocorticoid metabolism in the bovine cumulus–oocyte complex matured in vitro

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