Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.4.2.30 (PARP)
 13,611 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this study was to determine whether constitutive ErbB2 activation controls growth and apoptosis in colon cancer cells. Growth arrested GEO cells showed constitutive activation of ErbB2 in the absence of exogenous growth factors or serum supplementation. Higher levels of heregulin and ErbB2 activation were observed in the growth-arrested state and cell cycle re-entry was independent of exogenous growth factors. Blockade of ErbB2 activation by heregulin neutralizing antibodies and by AG879 resulted in prevention of cell cycle re-entry. This indicated that autocrine heregulin activity was responsible for growth factor independence and for cell cycle re-entry. Activation of ErbB2 was the result of heregulin mediated interaction with ErbB3 and generated downstream activation of the ERK and the PI3K/AKT pathways. Heregulin neutralizing antibody treatment of growth arrested GEO cells also generated apoptosis as reflected by PARP cleavage and DNA fragmentation indicating a cell survival signal was also induced by the constitutively activated ErbB2. The activation of AKT but not the MAPK pathway was responsible for cell survival in these cells.
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PMID:Autocrine heregulin generates growth factor independence and blocks apoptosis in colon cancer cells. 1179 Nov 78

Total knee arthroplasty (TKA) is the most common and cost-effective treatment for older adults with long-standing osteoarthritis. During TKA, muscle cells suffer from prolonged oxygen deficiency, which leads to altered cell metabolism that reduces the energy demand and maintains cell homeostasis before blood flow is restored. This study focused on the role of the lncRNA muscleblind-like 1 antisense RNA 1 (MBNL1-AS1) in protecting sevoflurane-pretreated mice against ischemia-reperfusion (I/R) injury after TKA, as well as the elucidation of the potential associated mechanism. Identification of differentially expressed lncRNAs was performed using the microarray dataset GSE21164, which was extracted from the GEO database. Target genes of the lncRNA were determined using Multi-Experiment Matrix (MEM), a dual-luciferase reporter gene assay, and KEGG enrichment analyses. The results showed that MBNL1-AS1 was overexpressed in skeletal muscle cells in mice, while KCNMA1, which was enriched in the cGMP-PKG signaling pathway, was negatively regulated by MBNL1-AS1. Furthermore, I/R mice displayed serious inflammatory reactions. Down-regulation of MBNL1-AS1 increased the expression of KCNMA1, PKGII, VASP, VEGF, Bcl-2, Cyclin D1, Cyclin D3, and Cdc 42 but decreased the expression of Bax, cleaved caspase-3, and cleaved PARP. Furthermore, upon MBNL1-AS1 upregulation, the rate of cell apoptosis increased while the rate of cell proliferation decreased. Our data suggested that down-regulated lncRNA MBNL1-AS1 might promote the proliferation and inhibit the apoptosis of skeletal muscle cells by upregulating KCNMA1 expression via activation of the cGMP-PKG signaling pathway, thus protecting sevoflurane-pretreated mice against I/R injury after TKA.
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PMID:Downregulation of the long noncoding RNA MBNL1-AS1 protects sevoflurane-pretreated mice against ischemia-reperfusion injury by targeting KCNMA1. 3018 81

Overactivation of androgen receptor (AR)-mediated signal has been extensively implicated in prostate cancer (CaP) development, progression, and recurrence, which makes it an attractive therapeutic target. Meanwhile, as an endogenous inhibitor of histone deacetylase 1 (HDAC 1), tumor-suppressive mammary serine protease inhibitor (maspin) was reported to sensitize drug-induced apoptosis with a better therapeutic outcome in CaP, but the relationship between AR and maspin remains unclear. In the current study, treatment of 5'-Aza or MS-275/enzalutamide induced poly (ADP-ribose) polymerase (PARP) cleavage and p-H2A.X in CaP cells with an increase of maspin expression but a decrease of AR. Then, treatment with protease inhibitor MG132 did not rescue the above drug-induced loss of AR. In addition, modulation of maspin expression by gene recombinant or siRNA technology showed an inverse correlation between expression of maspin and AR, consequently affecting the AR-regulated downstream gene transcription (e.g., NKX3.1 and TMPRSS2). Bioinformatics analysis of the data extracted from the National Center for Biotechnology Information Gene Expression Omnibus (NCBI GEO) database also revealed an inverse correlation between low maspin expression and high AR level in advanced CaP. Furthermore, chromatin immunoprecipitation (ChIP) assay using anti-maspin antibody identified that a portion of AR promoter sequence was co-precipitated and presented in the immunoprecipitated complex. Finally, maspin-mediated repression of AR was induced by treatment of MS-275, which promoted enzalutamide treatment efficacy with decrease of prostate-specific antigen (PSA) expression in LNCaP and 22RV1 cells. Taken together, the data not only demonstrated maspin-mediated repression of AR to augment drug anti-tumor activity but also provided in-depth support for combination of HDAC inhibitors with AR antagonist in CaP therapy.
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PMID:Tumor Suppressive Maspin-Sensitized Prostate Cancer to Drug Treatment Through Negative Regulating Androgen Receptor Expression. 3319 8