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      KCI등재

      Effects of BMI-1026, A Potent CDK Inhibitor, on Murine Oocyte Maturation and Metaphase II Arrest

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      https://www.riss.kr/link?id=A75265364

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      다국어 초록 (Multilingual Abstract)

      Previous studies have shown that BMI-1026 is a potent inhibitor of the cyclin-dependent kinases (cdk). In cell culture, the compound also arrests G2/M strongly and G1/S and S weakly. Two key kinases, cdk1 (p34cdc2 kinase) and mitogen-activated protein (MAP) kinase (erk1 and 2), perform crucial roles during oocyte maturation and, later, metaphase II (MII) arrest. In mammalian oocytes, both kinases are activated gradually around the time of germinal vesicle breakdown (GVBD) and maintain high activity in eggs arrested at metaphase II. In this study, we examined the effects of BMI-1026 on GVBD and MII arrest in mouse oocytes. BMI-1026 inhibited GVBD of immature oocytes and activated MII-arrested oocytes in a concentration-dependent manner, with more than 90% of oocytes exhibiting GVBD inhibition and MII activation at 100 nM. This is approximately 500~1,000 times more potent than the activity reported for the cdk inhibitors roscovitine (~50 M) and butyrolactone (~100 M). Based on the results of previous in vitro kinase assays, we expected BMI-1026 to inhibit only cdk1 activation in oocytes and eggs, not MAP kinase. However, in our cell-based system, it inhibited the activity of both kinases. We also found that the effect of BMI-1026 is reversible. Our results suggest that BMI-1026 inhibits GVBD and activates MII-arrested oocytes efficiently and reversibly and that it also inhibits both cdk1/histone H1 kinase and MAP kinase in mouse oocytes.
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      Previous studies have shown that BMI-1026 is a potent inhibitor of the cyclin-dependent kinases (cdk). In cell culture, the compound also arrests G2/M strongly and G1/S and S weakly. Two key kinases, cdk1 (p34cdc2 kinase) and mitogen-activated protein...

      Previous studies have shown that BMI-1026 is a potent inhibitor of the cyclin-dependent kinases (cdk). In cell culture, the compound also arrests G2/M strongly and G1/S and S weakly. Two key kinases, cdk1 (p34cdc2 kinase) and mitogen-activated protein (MAP) kinase (erk1 and 2), perform crucial roles during oocyte maturation and, later, metaphase II (MII) arrest. In mammalian oocytes, both kinases are activated gradually around the time of germinal vesicle breakdown (GVBD) and maintain high activity in eggs arrested at metaphase II. In this study, we examined the effects of BMI-1026 on GVBD and MII arrest in mouse oocytes. BMI-1026 inhibited GVBD of immature oocytes and activated MII-arrested oocytes in a concentration-dependent manner, with more than 90% of oocytes exhibiting GVBD inhibition and MII activation at 100 nM. This is approximately 500~1,000 times more potent than the activity reported for the cdk inhibitors roscovitine (~50 M) and butyrolactone (~100 M). Based on the results of previous in vitro kinase assays, we expected BMI-1026 to inhibit only cdk1 activation in oocytes and eggs, not MAP kinase. However, in our cell-based system, it inhibited the activity of both kinases. We also found that the effect of BMI-1026 is reversible. Our results suggest that BMI-1026 inhibits GVBD and activates MII-arrested oocytes efficiently and reversibly and that it also inhibits both cdk1/histone H1 kinase and MAP kinase in mouse oocytes.

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      목차 (Table of Contents)

      • ABSTRACT
      • INTRIDUSTION
      • MATERIALS AND METHODS
      • Collection of Oocytes and Eggs
      • Culture of Oocytes and Eggs
      • ABSTRACT
      • INTRIDUSTION
      • MATERIALS AND METHODS
      • Collection of Oocytes and Eggs
      • Culture of Oocytes and Eggs
      • Histone H1 and MBP Double-Kinase Assay
      • Evaluation of GVBD, Egg Activation and 2nd Polar Body Extrusion
      • Statistical Analysis
      • RESULTS
      • Effect of BMI-1026 on GVBD of Immature Oocytes
      • Effect of BMI-1026 on Histone H1 and MAP Kinases Activation
      • Effect of BMI-1026 on Activation of Ovulated Eggs
      • Reversibility of BMI-1026 on GVBD Inhibition
      • DISCUSSION
      • REFERENCES
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      참고문헌 (Reference)

      1 "p42/44 MAPKs are intracellular targets of the CDK inhibitor purvalanol" 21 : 6413-6424, 2002

      2 "Ubiquitin-proteasome pathway modulates mouse oocyte meiotic maturation and fertilization via regulation of MAPK cascade and cyclin B1 degradation" 121 : 1275-1287, 2004

      3 "The mechanism of CSF arrest in vertebrate oocytes" 187 : 173-178, 2002

      4 "The Mos/ mitogen-activated protein kinase (MAPK) pathway regulates the size and degradation of the first polar body in maturing mouse oocytes" 93 : 7032-7035, 1996a

      5 "Roscovitine, a specific inhibitor of cyclin-dependent protein kinases, reversibly inhibits chromatin condensation during in vitro maturation of porcine oocytes" 9 : 309-316, 2001

      6 "Protein synthesis and mRNA storage in cattle oocytes maintained under meiotic block by roscovitine inhibition of MPF activity" 69 : 457-467, 2004

      7 "Parthenogenetic activation of oocytes in c-mos-deficient mice" 68-370 71, 1994

      8 "Mos/mitogen-activated protein kinase can induce early meiotic phenotypes in the absence of maturation-promoting factor: a novel system for analyzing spindle formation during meiosis I" 93 : 4730-4735, 1996b

      9 "Mos is required for MAP kinase activation and is involved in microtubule organization during meiotic maturation in the mouse" 122 : 815-822, 1996

      10 "Microtubule and chromatin behavior follow MAP kinase activity but not MPF activity during meiosis in mouse oocytes" 1017-120 1025, 1994

      1 "p42/44 MAPKs are intracellular targets of the CDK inhibitor purvalanol" 21 : 6413-6424, 2002

      2 "Ubiquitin-proteasome pathway modulates mouse oocyte meiotic maturation and fertilization via regulation of MAPK cascade and cyclin B1 degradation" 121 : 1275-1287, 2004

      3 "The mechanism of CSF arrest in vertebrate oocytes" 187 : 173-178, 2002

      4 "The Mos/ mitogen-activated protein kinase (MAPK) pathway regulates the size and degradation of the first polar body in maturing mouse oocytes" 93 : 7032-7035, 1996a

      5 "Roscovitine, a specific inhibitor of cyclin-dependent protein kinases, reversibly inhibits chromatin condensation during in vitro maturation of porcine oocytes" 9 : 309-316, 2001

      6 "Protein synthesis and mRNA storage in cattle oocytes maintained under meiotic block by roscovitine inhibition of MPF activity" 69 : 457-467, 2004

      7 "Parthenogenetic activation of oocytes in c-mos-deficient mice" 68-370 71, 1994

      8 "Mos/mitogen-activated protein kinase can induce early meiotic phenotypes in the absence of maturation-promoting factor: a novel system for analyzing spindle formation during meiosis I" 93 : 4730-4735, 1996b

      9 "Mos is required for MAP kinase activation and is involved in microtubule organization during meiotic maturation in the mouse" 122 : 815-822, 1996

      10 "Microtubule and chromatin behavior follow MAP kinase activity but not MPF activity during meiosis in mouse oocytes" 1017-120 1025, 1994

      11 "Interplay between cdc2 kinase and MAP kinase pathway during maturation of mammalian oocytes" 49 : 461-469, 1998

      12 "Differential inactivation of maturation-promoting factor and mitogen-activated protein kinase following parthenogenetic activation of bovine oocytes" 59 : 537-545, 1998

      13 "Chromosome condensation pig oocytes: lack of a requirement for either cdc2 kinase or MAP" 63 : 110-118, 2002a

      14 "Characterization of a novel cyclin-dependent kinase 1 inhibitor, BMI-1026" 63 : 7384-7391, 2003

      15 "Butyrolactone I reversibly inhibits meiotic maturation of bovine oocytes without influencing chromosome condensation activity" 62 : 292-302, 2000

      16 "Biochemical and cellular effects of roscovitine, a potent and selective inhibitor of the cyclin-dependent kinases cdc2, cdk2, and cdk5" 243 : 527-536, 1997

      17 "Alterations and reversibility in the chromatin cytoskeleton and development of pig oocytes treated with roscovitine" 64 : 482-491, 2003

      18 "Activation of pig and cattle oocytes by butyrolactone I: morphological and biochemical study" 10 : 47-57, 2002b

      19 "Activation of p34cdc2 protein kinase activity in meiotic and mitotic cell cycles in mouse oocytes and embryos" 789-113 795, 1991

      20 "Activation of mitogen-activated protein kinase during meiotic maturation in mouse oocytes" 389-394, 1993

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      학술지 이력

      학술지 이력
      연월일 이력구분 이력상세 등재구분
      2019-03-14 학회명변경 한글명 : 한국수정란이식학회 -> 사단법인 한국동물생명공학회
      영문명 : The Korean Society Of Embryo Transfer -> The Korean Society of Animal Reproduction and Biotechnology
      2016 평가예정 신규평가 신청대상 (신규평가)
      2013-04-01 평가 탈락(현장점검) (기타)
      2010-01-01 평가 등재학술지 유지 (등재유지) KCI등재
      2007-01-01 평가 등재학술지 선정 (등재후보2차) KCI등재
      2006-01-01 평가 등재후보 1차 PASS (등재후보1차) KCI등재후보
      2005-03-21 학술지등록 한글명 : Reproductive & Developmental biology
      외국어명 : Reproductive & Developmental biology
      KCI등재후보
      2005-01-01 평가 등재후보학술지 유지 (등재후보1차) KCI등재후보
      2003-01-01 평가 등재후보학술지 선정 (신규평가) KCI등재후보
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