BioFactors

Cover image for Vol. 40 Issue 4

Edited By: Angelo Azzi

Impact Factor: 3.0

ISI Journal Citation Reports © Ranking: 2013: 57/123 (Endocrinology & Metabolism); 130/291 (Biochemistry & Molecular Biology)

Online ISSN: 1872-8081

Associated Title(s): Biochemistry and Molecular Biology Education, Biotechnology and Applied Biochemistry, IUBMB Life

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  • BMP growth factor signaling in a biomechanical context

    BMP growth factor signaling in a biomechanical context

    BMP-induced signaling cascades. BMP ligand binding to transmembrane receptors initiates Smad and non-Smad downstream signaling cascades that can be further classified into transcriptional and direct cellular responses. Smad activation, through phosphorylation by type I receptor, leads to trimeric complex formation and nuclear accumulation. In concerted activity with other transcription factors and general transcriptional regulators, Smads regulate gene transcription of multiple target genes. Furthermore, Smads possess “noncanonical” functions, as they bind to certain miRNAs and promote miRNA maturation. Non-Smad pathways include activation of p38, and JNK via TAB1/TAK1/XIAP protein complexes, or the activation of ERK and PKC/PKD through a yet unknown mechanism. Activation of PI3K leads to transcriptional regulation via Akt that can promote cell survival, or regulates direct cytoskeletal rearrangements via Rho GTPase dependent pathways.

  • The regulation of iron transport

    The regulation of iron transport

    The regulation of hepcidin production. The expression of hepcidin by hepatocytes is regulated by a complex network of signaling pathways. The best characterized is the BMP6/SMAD pathway. BMP6 production is induced by increasing iron stores. BMP6 binds to its receptor complex (BMPR) on the surface and induces the phosphorylation of SMADs 1, 5, and 8. These bind to SMAD4 and translocate to the nucleus where they induce hepcidin transcription. HJV acts as a co-receptor and forms part of the BMPR complex. The SMAD pathway also induces the expression of SMAD7, which interferes with SMAD signaling, and ID1, which induces the expression of matriptase 2, a protease that degrades HJV. Both of these systems act as negative feedback loops to reduce hepcidin production. HJV is also cleaved by furin to produce a soluble form that competes with membrane HJV for BMP6 binding. Inflammation induces hepcidin expression predominantly via IL-6 binding to its receptor (IL-6R) and stimulating the JAK/STAT pathway. Hepcidin is decreased during pregnancy, at least in part, by the binding of the estrogen/estrogen receptor complex to an estrogen responsive element in the hepcidin promoter. The decrease in hepcidin expression by the erythroid regulator is not well characterized, but it interferes with the BMP6/SMAD pathway, possibly via the detection of diferric transferrin levels by TFR1/HFE and TFR2. While hypoxia has been proposed to decrease hepcidin expression by affecting BMP6 signaling, it now seems likely that its effects are mediated by the erythroid regulator and are secondary to the effect of hypoxia on erythropoiesis.

  • Peroxynitrite, a potent macrophage-derived oxidizing cytotoxin to combat invading pathogens

    Peroxynitrite, a potent macrophage‐derived oxidizing cytotoxin to combat invading pathogens

    NADPH oxidase assembling. The NADPH oxidase is composed of three cytosolic (p67phox, p47phox, and p40phox) and two membrane-bound subunits (gp91phox and p22phox). Activation during phagocytosis leads to phosphorylation of cytosolic components and their migration to the membrane to form an active complex. Low doses of LPS or other stimuli, such as TNFα, are not sufficient to promote the oxidase activation, but lead to the primed state, increasing the phosphorylation level of cytosolic subunits.

  • Rho GTPases and cancer

    Rho GTPases and cancer

    Overview of tumor relevant functions of Rho GTPases. Simplified scheme showing major regulation and effector pathways of Rho GTPases in cancer with a focus on Rho, Rac, and Cdc42. Important effector pathways are indicated beside the corresponding arrows. Rho GTPases regulate invasion and metastasis particularly by controlling cytoskeletal organization. Rho GTPase-dependent gene expression controls stemness, angiogenesis, and immune response, while proliferation and survival are affected by cytoskeleton and gene expression. Rho-dependent cell contraction is important for microvesicle and CAF formation (RTKs: receptor tyrosine kinases; ROS: reactive oxygen species; CAF: cancer associated fibroblasts).

  • A DAF-16/FoxO3a-dependent longevity signal is initiated by antioxidants

    A DAF‐16/FoxO3a‐dependent longevity signal is initiated by antioxidants

    A new antiaging signaling pathway induced by oxidants or antioxidants. Treatment with antioxidants and/or the reduction of ROS levels by antioxidants results in the inactivation of PDK-1 by inhibiting its autophosphorylation. As a result, the levels of phosphorylation of SGK-1 and DAF-16/FOXO also decrease. Next, DAF-16/FoxO dissociates from the 14-3-3 proteins, translocates into the nucleus from the cytoplasm, and activates antiaging genes. Under oxidant stimulation, known JNK–MST signaling induces DAF-16/FoxO activation. Different activation form of DAF-16/FoxO by oxidant or antioxidant results in different works for lifespan extension of C. elegans.

  • Neuroprotective effects of resveratrol on damages of mouse cortical neurons induced by β-amyloid through activation of SIRT1/Akt1 pathway

    Neuroprotective effects of resveratrol on damages of mouse cortical neurons induced by β‐amyloid through activation of SIRT1/Akt1 pathway

    Effects of Aβ25–35 and resveratrol on neuron apoptosis. (A–C) The fluorescent images of the neurons stained with Hoechst 33342 (blue) and PI (red). In the control group, cells displayed normal nuclear morphology with uniform blue nuclei (A). While in Aβ25–35 injury group, the numbers of cell with bright red nuclei were obviously increased (B). And only few apoptotic cells were found when treated with 25 μM resveratrol (C). (D) Statistical analysis showed that, compared with the control group, neurons treated with Aβ25–35 exhibited greater apoptotic rate (*P < 0.01, n = 5), while when pre-incubated with resveratrol, the apoptotic rate could largely decreased (#P < 0.01, n = 5). Scale bars: A–C, 100 μm.

  • Urinary excretion of ginkgolide terpene lactones following acute consumption of Ginkgo biloba extract

    Urinary excretion of ginkgolide terpene lactones following acute consumption of Ginkgo biloba extract

    LC-MS-MS total ion count chromatogram of terpene lactones in 24 H urine following consumption of 240 mg ginkgo extract (high dose)/retention times (Min) of bilobalide (11.7), ethyl gallate (14.9), ginkgolide J (16.2), ginkgolide C (16.9), taxifolin (17.3), ginkgolide A (20.5), and ginkgolide B (21.2).

  • BMP growth factor signaling in a biomechanical context
  • The regulation of iron transport
  • Peroxynitrite, a potent macrophage‐derived oxidizing cytotoxin to combat invading pathogens
  • Rho GTPases and cancer
  • A DAF‐16/FoxO3a‐dependent longevity signal is initiated by antioxidants
  • Neuroprotective effects of resveratrol on damages of mouse cortical neurons induced by β‐amyloid through activation of SIRT1/Akt1 pathway
  • Urinary excretion of ginkgolide terpene lactones following acute consumption of Ginkgo biloba extract

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2014 BioFactors - Wiley Young Investigator Award

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On behalf of the IUBMB, BioFactors, and Wiley, it is with great pleasure and honor that we announce Juewon Kim as the recipient of the 2014 BioFactors - Wiley Young Investigator Award for his article, A DAF-16/FoxO3a-dependent longevity signal is initiated by antioxidants.

Mr. Kim is a Ph.D. candidate at the University of Tokyo in Chiba, Japan, where he earned a Masters Degree in Biological Sciences, and is a Senior Researcher at Amorepacific Inc. in the Beauty Food Research Institute where he conducts basic research for biological cosmetics as well as basic and applied research for functional food. He will be honored with the 2014 BioFactors - Wiley Young Investigator Award at the 15th IUBMB - 24th FAOBMB - TSBMB Conference this October 21 - 26, in Taipei, Taiwan, and his award-winning article will be FREELY available online through the conference.

Please join us in congratulating Mr. Kim as the recipient of the annual BioFactors – Wiley Young Investigator Award!

15th IUBMB - 24th FAOBMB - TSBMB International Conference, Taipei, Taiwan

Biochemistry and Molecular Biology in Transition: from Basic to Translational

15th IUBMB - 24th FAOBMB - TSBMB International Conference

Open Access Highlight

Click below to read this OnlineOpen Review Article in BioFactors for FREE:

Novel insights on interactions between folate and lipid metabolism
Robin P. da Silva, Karen B. Kelly, Ala Al Rajabi, René L. Jacobs
Volume 40, Issue 3, May/June 2014

Folate is an essential B vitamin required for the maintenance of AdoMet-dependent methylation. The liver is responsible for many methylation reactions that are used for post-translational modifications of proteins, methylation of DNA, and the synthesis of hormones, creatine, carnitine, and phosphatidylcholine. Conditions where methylation capacity is compromised, including folate deficiency, are associated with impaired phospatidylcholine synthesis resulting in non-alcoholic fatty liver disease and steatohepatitis. Read the full article FREE!

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