Disease relevance of butyrolactone i

• We studied the effects of butyrolactone I on the cell cycle as well as on phosphorylation of retinoblastoma protein (pRB) [1].
• Butyrolactone I inhibited phosphorylation of pRB catalyzed by cyclin A-cdk2 produced by baculovirus in vitro [1].
• An exogenous cdk inhibitor, butyrolactone-I, induces apoptosis with increased Bax/Bcl-2 ratio in p53-mutated pancreatic cancer cells [2].
• In the present study, the effect of butyrolactone I on expression of the albumin and alpha-fetoprotein (AFP) genes was investigated in HuH-7 human hepatoma cells [3].
• Antitumor effects of butyrolactone I, a selective cdc2 kinase inhibitor, on human lung cancer cell lines [4].

High impact information on butyrolactone i

• Caffeine reversed the DNA damage-induced inhibition of Cdc2 by causing dephosphorylation of Cdc2, and this dephosphorylation still occurred even when the Cdc2 feedback loops were blocked with butyrolactone-I [5].
• Consistent with this, Thr14/Tyr15 phosphorylation was induced when Cdc2 kinase activity was inhibited with butyrolactone-I [5].
• When PC12 cells were treated with specific inhibitors of cdc2/cdk2 (butyrolactone-I, olomoucin), they showed marked neurite extension and up-regulation of microtubule-associated protein 2 expression [6].
• When cells were treated with mimosine, a p53-independent p21-inducer, or butyrolactone I, a specific inhibitor of CDK, cellular endogenous p21 was induced and X-ray or adriamycin-induced apoptosis was blocked [7].
• The in vivo phosphorylation of E2F-1 was inhibited by butyrolactone I, a cyclin-dependent kinase inhibitor (Kitagawa et al., 1993, Oncogene, 8, 2425-2432) [8].

Biological context of butyrolactone i

• Fas-induced apoptosis was completely inhibited by butyrolactone I, a specific inhibitor of Cdc2 kinase [9].
• Thus butyrolactone I should be very useful for elucidating the function of cdc2 and cdk2 kinases in cell cycle regulation [10].
• However, butyrolactone I prevented Abeta-induced cell death only in neuronal cells in which cdk5 activation was sensitive to Abeta fibrils [11].
• In this study, the effects of CDK inhibitors (olomoucine, roscovitine, and butyrolactone I) on the Aplysia ocular circadian rhythm were investigated [12].
• Butyrolactone I specifically inhibits M-phase promoting factor activation and prevents the resumption of meiosis [13].

Anatomical context of butyrolactone i

• Roscovitine is a more selective cyclin-dependent kinase inhibitor; but, so is butyrolactone I, which did not prevent retinal ganglion cell death [14].
• A specific inhibitor of cdc2 kinase, butyrolactone I, inhibited phosphorylation of MAP4 both in mitotic HeLa cells and in the mitotic HeLa cell extract [15].
• However, by 44 h, 83.4% of butyrolactone I-treated oocytes reached MII compared with 88.6% of controls [13].
• Surprisingly, microinjections of butyrolactone I into the lateral septum or hippocampus significantly decreased baseline Cdk5 activity within the entire septo-hippocampal circuitry, suggesting a functional link between septal and hippocampal Cdk5 activity [16].
• The results suggested that although butyrolactone I reversibly inhibited germinal vesicle breakdown and mitogen-activated protein kinase activation, it did not affect mitochondrial and microfilament dynamics [13].

Associations of butyrolactone i with other chemical compounds

• We have tested the role of cyclin-dependent kinases (CDKs) in the type 3B death of axotomized retinal ganglion cells, by injecting intraocularly olomoucine, roscovitine, or butyrolactone I [17].
• Follicle-stimulating hormone-stimulated expansion and synthesis of hyaluronic acid (HA) by mouse OOX were assessed after 18 h of culture in media conditioned by porcine oocytes: 1) at different stages of maturation and 2) in which maturation was inhibited with a specific inhibitor of cdk-kinases, butyrolactone I [18].
• Treatment with Cdk inhibitor butyrolactone I induced the reduction of Chk1-S301 phosphorylation, although treatment with p38-specific inhibitor SB203580 or siRNA did not [19].
• This study suggests that 6-DMAP, cycloheximide, roscovitine and butyrolactone I can be use to block meiotic resumption in porcine oocytes in NCSU culture medium [20].
• Despite the different actions of milrinone and butyrolactone-I, the present study demonstrates that these reagents inhibit meiotic progression to a similar extent in the presence of FSH while maintaining developmental competence in porcine oocytes [21].

Gene context of butyrolactone i

• Butyrolactone I is a selective inhibitor of the cyclin-dependent kinase (cdk) family [1].
• In this work, we confirm the novel role of cyclin-dependent kinase (Cdk) 5 in associative learning by demonstrating that injection of the Cdk5 inhibitor butyrolactone I into the lateral septum or hippocampus profoundly impaired context-dependent fear conditioning of C57BL/6J mice [16].
• OA-induced MAPK activation was inhibited by butyrolactone I, an inhibitor of cyclin-dependent kinases 1 and 2 (CDK1, CDK2); thus, these kinases may regulate MAPK activity [22].
• We also found that butyrolactone I inhibits the CDK2 activity and enhances cell survival after an X-ray irradiation or doxorubicin treatment in both DLD1 (p21-/-) and DLD1 (p21+/+) cells [23].
• Butyrolactone I (BL) is a competitive inhibitor of ATP for binding and activation of cyclin-dependent kinases and is a potent inhibitor of cell cycle progression [24].

Analytical, diagnostic and therapeutic context of butyrolactone i

• Effects of butyrolactone I on mitogen-activated protein kinase activation and localization of microfilaments and active mitochondria were examined by Western blot analysis and laser scanning confocal microscopy, respectively [13].
• In this study, we have shown that butyrolactone I (BL-I), a potent inhibitor of cyclin-dependent kinases, affects oocyte cytoplasmic morphology and nuclear function in terms of nucleolar ultrastructure and immunocytochemistry [25].
• Butyrolactone I and cycloheximide effectively arrested/resumpted maturation; however, the oocytes percentages in metaphase II was the same for both cycloheximide and the control groups [26].
• By Northern blot analysis, the levels of both albumin and AFP mRNA were suppressed dose-dependently by butyrolactone I [3].
• Influence of meiotic inhibition by butyrolactone-I during germinal vesicle stage on the ability of porcine oocytes to be activated by electric stimulation after nuclear maturation [27].

References