BIOCHEMICAL PHARMACOLOGY
生化药理学
ISSN: 0006-2952
自引率: 3.4%
发文量: 306
被引量: 27929
影响因子: 6.094
通过率: 暂无数据
出版周期: 半月刊
审稿周期: 1.05
审稿费用: 0
版面费用: 暂无数据
年文章数: 306
国人发稿量: 83

投稿须知/期刊简介:

Biochemical Pharmacology is an international journal which publishes research findings in pharmacology deriving from investigations that employ the disciplines of biochemistry, biophysics, molecular biology, genetics, structural biology, computer models and/or physiology. Reports of studies with intact animals, organs, cells, subcellular components, enzymes or other cellular molecules and model systems are acceptable if they define mechanisms of drug action. Descriptive mathematical models including those involving computer techniques are also welcome. Experiments involving the use of drugs to elucidate physiological and behavioral mechanisms in living organisms are also within the scope of the journal. In general, papers that record concentrations of drugs and metabolites in body fluids will only be accepted if they contribute to an understanding of biochemical and biophysical mechanisms. The Editors, however, reserve the right to publish any papers of major interest in the field. Only contributions in English will be considered or published. The journal publishes the following types of communications (1) Full-length Papers. These consist of a body of work presenting original findings relating to the question proposed by the investigators undertaking the research. (2) Short Communications. These consist of an original body of work of narrower scope but of the same quality as the above. By definition, these papers are shorter than full-length manuscripts. (3) Rapid Communications. These promote rapid dissemination of timely and significant observations within the scope of the journal. Manuscripts must be submitted in English and will be judged as appropriate for publication as rapid communications on the basis of their immediate importance. They should be written to emphasize clearly the novel aspects of the research. These criteria will be applied strictly. (4) Commentaries are short commissioned review articles (3000-5000 words in length). They are designed to be editorial statements on selected topics, and should not be exhaustive reviews. Primarily, Commentaries are intended to stimulate thought. They can be controversial, and can either focus on areas subject to much activity, or draw attention to relatively neglected fields in which there is both the opportunity and the need for research in biochemical pharmacology. Particularly welcome will be Commentaries in which authors present their personal view on the state of the subject on which they are reporting, and give their view as to where in the near or distant future the subject may be moving. Authors are especially encouraged to take issue with popular dogmas.

期刊描述简介:

Biochemical Pharmacology is an international journal which publishes research findings in pharmacology deriving from investigations that employ the disciplines of biochemistry, biophysics, molecular biology, genetics, structural biology, computer models and/or physiology. Reports of studies with intact animals, organs, cells, subcellular components, enzymes or other cellular molecules and model systems are acceptable if they define mechanisms of drug action. Descriptive mathematical models including those involving computer techniques are also welcome. Experiments involving the use of drugs to elucidate physiological and behavioral mechanisms in living organisms are also within the scope of the journal. In general, papers that record concentrations of drugs and metabolites in body fluids will only be accepted if they contribute to an understanding of biochemical and biophysical mechanisms. The Editors, however, reserve the right to publish any papers of major interest in the field. Only contributions in English will be considered or published. The journal publishes the following types of communications (1) Full-length Papers. These consist of a body of work presenting original findings relating to the question proposed by the investigators undertaking the research. (2) Short Communications. These consist of an original body of work of narrower scope but of the same quality as the above. By definition, these papers are shorter than full-length manuscripts. (3) Rapid Communications. These promote rapid dissemination of timely and significant observations within the scope of the journal. Manuscripts must be submitted in English and will be judged as appropriate for publication as rapid communications on the basis of their immediate importance. They should be written to emphasize clearly the novel aspects of the research. These criteria will be applied strictly. (4) Commentaries are short commissioned review articles (3000-5000 words in length). They are designed to be editorial statements on selected topics, and should not be exhaustive reviews. Primarily, Commentaries are intended to stimulate thought. They can be controversial, and can either focus on areas subject to much activity, or draw attention to relatively neglected fields in which there is both the opportunity and the need for research in biochemical pharmacology. Particularly welcome will be Commentaries in which authors present their personal view on the state of the subject on which they are reporting, and give their view as to where in the near or distant future the subject may be moving. Authors are especially encouraged to take issue with popular dogmas.

最新论文
  • 12(S)-hydroxyheptadeca-5Z,8E,10E-trienoic acid (12-HHT) induces cell growth and improves barrier function through BLT2 interaction in intestinal epithelial Caco-2 cell cultures.

    12(S)-hydroxyheptadeca-5Z,8E,10E-trienoic acid (12-HHT) is an unusual product of the cyclooxygenase pathway that is an endogenous ligand of the low-affinity receptor for leukotriene 4 (LTB), BLT2. Recent findings suggested that BLT2 possibly plays an important role in the healing of intestinal lesions and the regulation of barrier function. Here, we studied the role of 12-HHT on intestinal epithelial cell growth and the paracellular permeability of intestinal epithelium using Caco-2 cell cultures as experimental model. Our results demonstrated that 12-HHT stimulates intestinal epithelial Caco-2 cell growth through 12-HHT-BLT2-p38-PKC axis and improves paracellular permeability in differentiated Caco-2 cell cultures through the regulation of tight junction elements such as myosin light chain phosphorylation through 12-HHT-BLT2-p38-PKC-MYPT1 axis. Thus, 12-HHT-BLT2 interaction can be involved in intestinal epithelial cell growth and consequently in the epithelium regeneration/repair processes, together with an interesting improvement on the paracellular permeability. These effects appoint that 12-HHT/BLT2 axis may be a suitable strategy for treating wound healing epithelium and barrier-disrupted intestinal processes.

    被引量:- 发表:1970

  • Pregnane-X-receptor mediates the anti-inflammatory activities of rifaximin on detoxification pathways in intestinal epithelial cells.

    The pregnane-X-receptor (PXR) is master gene overseeing detoxification of wide number of xenobiotics and is critical for maintenance of intestinal integrity. The intestinal expression of genes involved in cellular detoxification is down-regulated in patients with inflammatory bowel diseases (IBD). Rifaximin is a non-absorbable antibiotic endowed with a PXR agonistic activity. In the present study we have investigated whether rifaximin activates PXR in primary human colon epithelial cells and human colon biopsies and assessed whether this antibiotic antagonizes the effect of tumor necrosis factor (TNF)-α on expression of PXR and PXR-related genes. Present results demonstrate that primary colon epithelial cells express PXR and that their exposure to rifaximin induces the expression of genes involved in cellular detoxification. Exposure to TNFα reduces the expression of PXR mRNA as well as expression of its target genes. This inhibitory effect was prevented by that co-treatment with rifaximin. Knocking down the expression of PXR in colon epithelial cells by an anti-PXR siRNA, abrogated the counter-regulatory effects exerted by rifaximin on cell exposed to TNFα. Finally, ex vivo exposure of colon biopsies obtained from ulcerative colitis patients to rifaximin increased the expression of genes involved in xenobiotics metabolism. In aggregate, these data illustrate that rifaximin increases the expression of PXR and PXR-regulated genes involved in the metabolism and excretion of xenobiotics and antagonizes the effects of TNFα in intestinal epithelial cells and colon biopsies. These non-antibiotic effects of rifaximin could contribute to the maintenance of the intestinal barrier integrity against xenobiotics and products generated by luminal bacteria.

    被引量:49 发表:1970

  • Cadmium induces apoptotic cell death in WI 38 cells via caspase-dependent Bid cleavage and calpain-mediated mitochondrial Bax cleavage by Bcl-2-independent pathway.

    Previous reports have demonstrated that cadmium (Cd) may induce cell death via apoptosis, but the mechanism responsible for cellular death is not clear. In this study, we investigated the signaling pathways implicated in Cd-induced apoptosis in lung epithelial fibroblast (WI 38) cells. Apoptotic features were observed using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay, propidium iodide staining and DNA laddering. A treatment of cadmium caused the caspase-8-dependent Bid cleavage, the release of cytochrome c (Cyt c), activation of caspase-9 and -3, and PARP cleavage. A caspase-8 specific inhibitor prevented the Bid cleavage, caspase-3 activation and cell death. Alternatively, we observed that full-length Bax was cleaved into 18-kDa fragment (p18/Bax); this was initiated after 12 h and by 36 h the full-length Bax protein was totally cleaved to the p18/Bax, which caused a drastic release of Cyt c from mitochondria. The p18/Bax was detected exclusively in the mitochondrial fraction, and it originated from mitochondrial full-length Bax, but not from the cytosol full-length Bax. Cd also induced the activation of the mitochondrial 30-kDa small subunit of calpain that was preceded by Bax cleavage. Cd induced the upregulation of Bcl-2 and the degradation of p53 protein. N-acetyl cysteine effectively inhibited the Cd-induced DeltaPsim reduction, indicating ROS acts upstream of mitochondrial membrane depolarization. Taken together, our results suggest that Cd-induced apoptosis was thought to be mediated at least two pathways; caspase-dependent Bid cleavage, and the other is calpain-mediated mitochondrial Bax cleavage. Moreover, we found that the function of Bid and Bax was not dependent of Bcl-2, and that ROS can also contribute in the Cd-induced cell death.

    被引量:- 发表:2004

  • Functional analysis of activation and repression domains of the rainbow trout aryl hydrocarbon receptor nuclear translocator (rtARNT) protein isoforms.

    The aryl hydrocarbon receptor nuclear translocator (ARNT) protein is involved in many signaling pathways. Rainbow trout express isoforms of ARNT protein that are divergent in their C-terminal domains due to alternative RNA splicing. Rainbow trout ARNT(b) (rtARNT(b)) contains a C-terminal domain rich in glutamine and asparagine (QN), whereas the C-terminal domain of rtARNT(a) is rich in proline, serine, and threonine (PST). rtARNT(b) functions positively in AH receptor-mediated signaling, whereas rtARNT(a) functions negatively. Studies were performed to understand how changes in the C-terminal domains of the two rtARNT isoforms affect function. Deletion of the QN-rich C-terminal domain of rtARNT(b) did not affect function in aryl hydrocarbon receptor (AHR)-mediated signaling, whereas deletion of the PST-rich domain of rtARNT(a) restored function. Expression of the PST-rich domain on truncated rtARNT(b) or mouse ARNT (mARNT) reduced function of this protein by 50-80%. Gel shift assays revealed that the PST-rich domain affected AHR-mediated signaling by inhibiting DNA binding of the AHR*ARNT heterodimer. Gal4 transactivation assays revealed a potent transactivation domain in the QN-rich domain of rtARNT(b). In contrast, Gal4 proteins containing the PST-rich domain of rtARNT(a) did not transactivate because the proteins did not bind to DNA. Secondary structure analysis of the PST-rich domain revealed hydrophilic and hydrophobic regions. Truncation of the hydrophobic domain that spanned the final 20-40 amino acids of the rtARNT(a) restored function to the protein, suggesting that repressor function was related to protein misfolding or masking of the basic DNA binding domain. Functional diversity within the C-terminal domain is consistent with other negatively acting transcription factors and illustrates a common biological theme.

    被引量:1 发表:1999

  • Characterization of a novel adenosine binding protein sensitive to cyclic AMP in rat brain cytosolic and particulate fractions.

    A novel binding site for the adenosine receptor agonist 5'-N-ethylcarboxamidoadenosine (NECA), which was enriched in rat forebrain, was characterized in cytosolic and particulate preparations. The site showed a pharmacological profile different from other [3H]NECA binding proteins and was named adenotin 2. [3H]NECA was bound in the presence of 100 microM 2-chloroadenosine with a Kd of 45.4 nM and a Bmax of 4711 fmol/mg in the cytosol and a Kd of 72.4 nM and a Bmax of 4844 fmol/mg in the crude membrane fraction. The presence of two different binding sites on adenotin 2 for [3H]NECA was shown in kinetic experiments. This protein showed identical pharmacological profiles in both subcellular preparations. [3H]NECA was displaced by purine analogues with a rank order of potency of NECA > 3'5' cyclic AMP (cAMP) > 5'-deoxy-5'-chloroadenosine > S-adenosylhomocysteine approximately 5'-deoxy-5'-methylthioadenosine (MeSA) > adenosine approximately adenine. cAMP inhibited [3H]NECA binding allosterically, whereas adenine and MeSA acted competitively. Inhibitors and activators of protein kinases such as N-(2-aminoethyl)-5-isoquinolinesulfonamide, Sp-adenosine cyclic monophophothioate and (8R*, 9S*, 11S*)-(-)-9-hydroxy-9-methoxy -carbonyl-8-methyl-2,3,9, 10-tetrahydro-8,11-epoxy-1H, 8H, 11H-2, 7b, 11a-triazadibenzo-(a,g)cycloocta(cde)-trinden-1-one (K 252a) interacted with [3H]NECA binding to adenotin 2 in nanomolar concentrations. Adenosine-5'-O-(3-thiotriphosphate) (100 microM) increased the affinity of [3H]NECA to a Kd of 9 nM and diminished the affinity of cAMP. The pharmacological characteristics of this novel binding site for [3H]NECA resemble those of the inhibition of phosphorylation processes by adenosine and its derivatives in heart and smooth muscle but are distinct from known adenosine receptors, adenosine binding proteins and protein kinases.

    被引量:1 发表:1996

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