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1.
Hironori ABE Ryosuke SAKUMOTO Kiyoshi OKUDA 《The Journal of reproduction and development》2015,61(4):277-286
We recently demonstrated that luteal cells flow out from the ovary via lymphatic vessels during luteolysis. However, the regulatory mechanisms of the outflow of luteal cells are not known. Matrix metalloproteinases (MMPs) can degrade the extracellular matrix and basal membrane, and tissue inhibitors of matrix metalloproteinases (TIMPs) inhibit the activity of MMPs. To test the hypothesis that MMP expression in luteal cells is regulated by luteolytic factors, we investigated the effects of prostaglandin F2α (PGF), interferon γ (IFNG) and tumor necrosis factor α (TNF) on the mRNA expression of MMPs and TIMPs in cultured luteal cells. Luteal cells obtained from the CL at the mid-luteal stage (days 8–12 after ovulation) were cultured with PGF (0.01, 0.1, 1 μM), IFNG (0.05, 0.5, 5 nM) and TNF (0.05, 0.5, 0.5 nM) alone or in combination for 24 h. PGF and IFNG significantly increased the expression of MMP-1 mRNA. In addition, 1 μM PGF in combination with 5 nM IFNG
stimulated MMP-1 and MMP-9 mRNA expression significantly more than either treatment alone. In contrast, IFNG significantly decreased the level of MMP-14 mRNA. The mRNA expression of TIMP-1, which preferentially inhibits MMP-1, was suppressed by 5 nM INFG. One μM PGF and 5 nM IFNG suppressed TIMP-2 mRNA expression. These results suggest a new role of MMPs: luteal MMPs stimulated by PGF and IFNG break down the extracellular matrix surrounding luteal cells, which accelerates detachment from the CL during luteolysis, providing an essential prerequisite for outflow of luteal cells from the CL to lymphatic vessels. 相似文献
2.
Satoshi KAMBAYASHI Masaya IGASE Kosuke KOBAYASHI Ayana KIMURA Takako SHIMOKAWA MIYAMA Kenji BABA Shunsuke NOGUCHI Takuya MIZUNO Masaru OKUDA 《The Journal of veterinary medical science / the Japanese Society of Veterinary Science》2015,77(11):1405-1412
Hypoxic conditions in various cancers are believed to relate with their
malignancy, and hypoxia inducible factor-1α (HIF-1α) has been shown to be a major
regulator of the response to low oxygen. In this study, we examined HIF-1α expression in
canine lymphoma using cell lines and clinical samples and found that these cells expressed
HIF-1α. Moreover, the HIF-1α inhibitors, echinomycin, YC-1 and 2-methoxyestradiol,
suppressed the proliferation of canine lymphoma cell lines. In a xenograft model using
NOD/scid mice, echinomycin treatment resulted in a dose-dependent regression of the tumor.
Our results suggest that HIF-1α contributes to the proliferation and/or survival of canine
lymphoma cells. Therefore, HIF-1α inhibitors may be potential agents to treat canine
lymphoma. 相似文献
3.
Yuki YAMAMOTO Yoshihiko KOBAYASHI Kiyoshi OKUDA 《The Journal of reproduction and development》2014,60(1):73-77
Isolated stromal cells from the ampullary and isthmic parts of bovine oviductal tissues
were cultured in monolayer and spheroid (cell aggregate) systems. Prostaglandin F2α (PGF)
plays a crucial role in oviductal contraction and is produced by oviductal epithelial
cells in cattle. Since stromal cells of many organs produce PGF, PGF production by bovine
oviductal stromal cells was investigated. After PGF synthesis was confirmed, the utility
of isolation and culture methods for oviductal stromal cells was evaluated by PGF
production in the present study. The homogeneity of the cells was > 99%. PGF production
of the cells was increased by tumor necrosis factor-α. The stromal cells aggregated and
formed a spheroid by the treatments with several reagents. PGF production was higher in
the spheroid culture than in the monolayer culture. The isolation and culture methods
described here will facilitate studies of the physiological function of bovine oviductal
stromal cells. 相似文献
4.
Yasunaga YOSHIKAWA Masami MORIMATSU Kazuhiko OCHIAI Toshina ISHIGURO-OONUMA Ryo MORIOKA Kento OKUDA Koichi ORINO 《The Journal of veterinary medical science / the Japanese Society of Veterinary Science》2021,83(5):759
Mammary tumors are the most common tumors in women and non-spayed female dogs. One of the reasons for mammary tumors is mutations of the tumor suppressor gene, BRCA2. BRCA2 participates in homologous recombination repair by interacting with the RAD51 recombinase. BRCA2 has two RAD51-binding domains, consisting of BRC repeats and the C-terminal RAD51-binding domain, respectively. Although several studies have addressed the function of the C-terminal RAD51-binding domain of human BRCA2, the amino acid sequences required for the RAD51-interaction activity remain unclear. In this study, the C-terminal RAD51-binding domains of canine and human BRCA2 were compared; the canine domain displayed a weaker interaction with RAD51. This difference was attributed to the C-terminal portion of the domain via a comparison between canine and human domains. Furthermore, peptides shorter than those previously reported displayed RAD51-interacting activity, and a core motif of this domain consisting of 25 amino acids was identified. Since a mutation (S3323N) was reported in the core motif of this domain, the effect of this mutation was evaluated. The mutant exhibited similar RAD51-binding activity as that of the wild-type protein, suggesting that the mutation was functionally neutral. These data suggested that the C-terminal portion of the BRCA2 C-terminal RAD51-binding domain influenced its RAD51-interaction activity, and a minimum core motif of 25 amino acids was identified in this domain. These data may help clarify BRCA2 function, as well as the tumorigenic effects of BRCA2 mutation. 相似文献
5.
When animals do not become pregnant, regression of the corpus luteum (CL) is essential for normal cyclicity because it allows the development of a new ovulatory follicle. Luteal regression is caused by a pulsatile release of prostaglandin (PG) F2α from the uterus in the late luteal phase in most mammals including cattle. Although it has been proposed in ruminants that pulsatile PGF2α secretion is generated by a positive feedback loop between luteal and/or hypophyseal oxytocin and uterine PGF2α, the bovine endometrium may possess other mechanisms for initiation of luteolytic PGF2α secretion. There is increasing evidence that several cytokines mainly produced by immune cells modulate CL and uterine function in many species. Tumor necrosis factor‐α (TNF‐α) stimulates PGF2α output from bovine endometrium not only at the follicular phase but also at the late luteal phase. Administration of TNF‐α at a high concentration prolongs luteal lifespan, whereas administration of a low concentration of TNF‐α accelerates luteal regression in cows. The data obtained from the authors’ previous in vitro and in vivo studies strongly suggest that TNF‐α is a crucial factor in regulating luteolysis in cows. The authors’ recent study has shown that interleukin‐1α mediates PG secretion from bovine endometrium as a local regulator. Furthermore, interferon‐τ (IFN‐τ) suppresses the action of TNF‐α on PGF2α synthesis by the bovine endometrium in vitro, suggesting that IFN‐τ plays a luteoprotective role by inhibiting TNF‐α‐induced PGF2α production in early pregnancy. The purpose of the present review is to summarize current understanding of the endocrine mechanisms that regulate uterine function by cytokines during the estrous cycle and early pregnancy in cows. 相似文献
6.
Nakahara K Fukui K Murakami N 《The Journal of veterinary medical science / the Japanese Society of Veterinary Science》2004,66(10):1297-1300
To investigate which brain regions are involved in the anticipatory activity in rats restricted feeding for 2 hr, we examined c-Fos expression before and after feeding. Only the thalamic paraventricular nucleus (tPVN) showed c-Fos expression before feeding than after feeding. After the anticipatory locomotor activity rhythm was established, lesioning the tPVN attenuated this rhythm, but not the light-dark entrained rhythm. The anticipatory increase of blood corticosterone levels was not established in long-term tPVN-lesioned rats. These results suggest that the tPVN is involved in the expression of anticipatory reactions under a food-restricted regimen. 相似文献
7.
Syota KAWAGUCHI Ryosuke SAKUMOTO Kiyoshi OKUDA 《The Journal of reproduction and development》2013,59(3):219-224
Luteoprotective mechanisms of luteinizing hormone (LH) involved in the maintenance of
bovine corpus luteum (CL) function have not been completely clarified. Since antioxidant
enzymes are well documented as antiapoptotic factors in the CL of many mammals, we
hypothesized that the luteoprotective action of LH is mediated by stimulating the local
production and action of antioxidant enzymes. To test the above hypothesis, in the present
study, we examined the mechanisms involved in the luteoprotective actions of LH. Cultured
bovine luteal cells obtained from the CL at the mid-luteal stage (days 8–12 of the estrous
cycle) were treated with LH (10 ng/ml), onapristone (OP; a specific progesterone receptor
antagonist, 100 μM) and diethyldithiocarbamate [DETC; an inhibitor of superoxide dismutase
(SOD), 100 μM] for 24 h. LH in combination with or without OP significantly increased the
mRNA and protein expressions of manganese SOD (Mn-SOD) and catalase (CATA) and SOD
activity. While LH alone significantly increased the mRNA and protein
expressions of SOD containing copper and zinc (Cu,Zn-SOD), OP in combination with or
without LH significantly decreased the mRNA and protein expressions of Cu,Zn-SOD. In
addition, Cu,Zn-SOD, Mn-SOD and CATA mRNA expressions were higher at the mid luteal phase
than the other luteal phases. LH in combination with DETC significantly decreased
LH-increased cell viability. The overall results suggest that LH increases cell viability
by LH-increased antioxidant enzymes, resulting in maintenance of CL function during the
luteal phase in cattle. 相似文献
8.
Masahiko Mori Kento Maki Tsubasa Kawahata Daigo Kawahara Yuta Kato Toru Yoshida Hidetaka Nagasawa Hitoshi Sato Atsushi J. Nagano Paul C. Bethke Kiyoaki Kato 《Breeding Science》2021,71(2):208
Epicotyl length (ECL) of adzuki bean (Vigna angularis) affects the efficiency of mechanized weeding and harvest. The present study investigated the genetic factors controlling ECL. An F2 population derived from a cross between the breeding line ‘Tokei1121’ (T1121, long epicotyls) and the cultivar ‘Erimo167’ (common epicotyls) was phenotyped for ECL and genotyped using simple sequence repeats (SSRs) and single-nucleotide polymorphism (SNP) markers. A molecular linkage map was generated and fifty-two segregating markers, including 27 SSRs and 25 SNPs, were located on seven linkage groups (LGs) at a LOD threshold value of 3.0. Four quantitative trait loci (QTLs) for ECL, with LOD scores of 4.0, 3.4, 4.8 and 6.4, were identified on LGs 2, 4, 7 and 10, respectively; together, these four QTLs accounted for 49.3% of the phenotypic variance. The segregation patterns observed in F5 residual heterozygous lines at qECL10 revealed that a single recessive gene derived from T1121 contributed to the longer ECL phenotype. Using five insertion and deletion markers, this gene was fine mapped to a ~255 kb region near the end of LG10. These findings will facilitate marker-assisted selection for breeding in the adzuki bean and contribute to an understanding of the mechanisms associated with epicotyl elongation. 相似文献
9.
Mariko KUSE Hwa-Yong LEE Tomas J. ACOSTA Takuo HOJO Kiyoshi OKUDA 《The Journal of reproduction and development》2013,59(4):346-352
Cortisol (Cr), the most important glucocorticoid (GC), is well known to suppress uterine
prostaglandin F2α (PGF) production. However, the details of the regulatory mechanisms
controlling the cyclic changes in endometrial PGF production remain unclear. Here we
investigated the expression of the GC receptor (GC-Rα), the actions of cortisol throughout
the estrous cycle and the regulatory mechanism of GC-Rα in the bovine endometrium. The
levels of GC-Rα protein were greater at the mid-luteal stage (Days 8–12) than at the other
stages. Cr more strongly suppressed PGF production at the mid-luteal stage than at the
follicular stage. GC-Rα expression was increased by progesterone (P4) but decreased by
estradiol-17β (E2) in cultured endometrial stromal cells. The overall results suggest that
ovarian steroid hormones control the cyclic changes in endometrial PGF production by
regulating GC-Rα expression in bovine endometrial stromal cells. 相似文献
10.