What's in a Name? [Editorial]
(Source: FASEB Journal)
Source: FASEB Journal - August 1, 2017 Category: Biology Tags: Editorial Source Type: research
Erratum [Erratum]
(Source: FASEB Journal)
Source: FASEB Journal - June 29, 2017 Category: Biology Tags: Erratum Source Type: research
Critical role for complement receptor C5aR2 in the pathogenesis of renal ischemia-reperfusion injury [Research]
The complement system, and specifically C5a, is involved in renal ischemia-reperfusion (IR) injury. The 2 receptors for complement anaphylatoxin C5a (C5aR1 and C5aR2) are expressed on leukocytes as well as on renal epithelium. Extensive evidence shows that C5aR1 inhibition protects kidneys from IR injury; however, the role of C5aR2 in IR injury is less clear as initial studies proposed the hypothesis that C5aR2 functions as a decoy receptor. By Using wild-type, C5aR1–/–, and C5aR2–/– mice in a model of renal IR injury, we found that a deficiency of either of these receptors protected mice from renal...
Source: FASEB Journal - June 29, 2017 Category: Biology Authors: Poppelaars, F., van Werkhoven, M. B., Kotimaa, J., Veldhuis, Z. J., Ausema, A., Broeren, S. G. M., Damman, J., Hempel, J. C., Leuvenink, H. G. D., Daha, M. R., van Son, W. J., van Kooten, C., van Os, R. P., Hillebrands, J.-L., Seelen, M. A. Tags: Research Source Type: research
Nuclear complex of glyceraldehyde-3-phosphate dehydrogenase and DNA repair enzyme apurinic/apyrimidinic endonuclease I protect smooth muscle cells against oxidant-induced cell death [Research]
Atherosclerotic plaque destabilization is the major determinant of most acute coronary events. Smooth muscle cell (SMC) death contributes to plaque destabilization. Here, we describe a novel antiapoptotic mechanism in vascular SMCs that involves interaction of nuclear glyceraldehyde-3-phosphate dehydrogenase (GAPDH) with apurinic/apyrimidinic endonuclease 1 (Ape1), the major oxidized DNA repair enzyme. GAPDH down-regulation potentiated H2O2-induced DNA damage and SMC apoptosis. Conversely, GAPDH overexpression decreased DNA damage and protected SMCs against apoptosis. Ape1 down-regulation reversed the resistance of GAPDH-o...
Source: FASEB Journal - June 29, 2017 Category: Biology Authors: Hou, X., Snarski, P., Higashi, Y., Yoshida, T., Jurkevich, A., Delafontaine, P., Sukhanov, S. Tags: Research Source Type: research
A novel tarantula toxin stabilizes the deactivated voltage sensor of bacterial sodium channel [Research]
In this study, we sought to identify peptide toxins stabilizing the deactivated VSM of bacterial NaVs. We screened fractions from several venoms and characterized a cystine knot toxin called JZTx-27 from the venom of tarantula Chilobrachys jingzhao as a high-affinity antagonist of the prokaryotic NaVs NsVBa (nonselective voltage-gated Bacillus alcalophilus) and NaChBac (bacterial sodium channel from Bacillus halodurans) (IC50 = 112 nM and 30 nM, respectively). JZTx-27 was more efficacious at weaker depolarizing voltages and significantly slowed the activation but accelerated the deactivation of NsVBa, whereas the local ane...
Source: FASEB Journal - June 29, 2017 Category: Biology Authors: Tang, C., Zhou, X., Nguyen, P. T., Zhang, Y., Hu, Z., Zhang, C., Yarov-Yarovoy, V., DeCaen, P. G., Liang, S., Liu, Z. Tags: Research Source Type: research
Novel selective {beta}1-adrenoceptor antagonists for concomitant cardiovascular and respiratory disease [Research]
β-Blockers reduce mortality and improve symptoms in people with heart disease; however, current clinically available β-blockers have poor selectivity for the cardiac β1-adrenoceptor (AR) over the lung β2-AR. Unwanted β2-blockade risks causing life-threatening bronchospasm and reduced efficacy of β2-agonist emergency rescue therapy. Thus, current life-prolonging β-blockers are contraindicated in patients with both heart disease and asthma. Here, we describe NDD-713 and -825, novel highly β1-selective neutral antagonists with good pharmaceutical properties that can potentially overcome...
Source: FASEB Journal - June 29, 2017 Category: Biology Authors: Baker, J. G., Gardiner, S. M., Woolard, J., Fromont, C., Jadhav, G. P., Mistry, S. N., Thompson, K. S. J., Kellam, B., Hill, S. J., Fischer, P. M. Tags: Research Source Type: research
Pharmacological Sirt6 inhibition improves glucose tolerance in a type 2 diabetes mouse model [Research]
This study represents the first in vivo study of a SIRT6 inhibitor and provides the proof-of-concept that targeting SIRT6 may be a viable strategy for improving glycemic control in T2DM.—Sociali, G., Magnone, M., Ravera, S., Damonte, P., Vigliarolo, T., Von Holtey, M., Vellone, V. G., Millo, E., Caffa, I., Cea, M., Parenti, M. D., Del Rio, A., Murone, M., Mostoslavsky, R., Grozio, A., Nencioni, A., Bruzzone S. Pharmacological Sirt6 inhibition improves glucose tolerance in a type 2 diabetes mouse model. (Source: FASEB Journal)
Source: FASEB Journal - June 29, 2017 Category: Biology Authors: Sociali, G., Magnone, M., Ravera, S., Damonte, P., Vigliarolo, T., Von Holtey, M., Vellone, V. G., Millo, E., Caffa, I., Cea, M., Parenti, M. D., Del Rio, A., Murone, M., Mostoslavsky, R., Grozio, A., Nencioni, A., Bruzzone, S. Tags: Research Source Type: research
NAADP-mediated Ca2+ signaling promotes autophagy and protects against LPS-induced liver injury [Research]
LPS has been shown to induce hepatocyte autophagy, but little is known about how LPS is able to do this during acute toxic liver injury. Our aim was to determine the existence of any selective Ca2+ signaling coupling to hepatocyte autophagy in response to LPS. LPS increased the autophagic process in hepatocytes, and CD38 knockdown prevented this response. Ned19, a specific inhibitor for nicotinic acid adenine dinucleotide phosphate (NAADP), prevented LPS-mediated Ca2+ signaling and autophagosome formation in hepatocytes. CD38 overexpression protected the liver from LPS/d-galactosamine (GalN)-induced injury, and NAADP admin...
Source: FASEB Journal - June 29, 2017 Category: Biology Authors: Rah, S.-Y., Lee, Y.-H., Kim, U.-H. Tags: Research Source Type: research
LEF1-mediated MMP13 gene expression is repressed by SIRT1 in human chondrocytes [Research]
In this study, we assessed the role of SIRT1 in LEF1-mediated MMP13 gene expression in human OA chondrocytes. Results showed that MMP13 protein levels and enzymatic activity decreased significantly during SIRT1 overexpression or activation by resveratrol. Conversely, MMP13 gene expression was reduced in chondrocytes transfected with SIRT1 siRNA or treated with nicotinamide (NAM), a sirtuin inhibitor. Chondrocytes challenged with IL-1β, a cytokine involved in OA pathogenesis, enhanced LEF1 protein levels and gene expression, resulting in increased MMP13 gene expression; however, overexpression of SIRT1 during IL-1&beta...
Source: FASEB Journal - June 29, 2017 Category: Biology Authors: Elayyan, J., Lee, E.-J., Gabay, O., Smith, C. A., Qiq, O., Reich, E., Mobasheri, A., Henrotin, Y., Kimber, S. J., Dvir-Ginzberg, M. Tags: Research Source Type: research
Cyclic dinucleotides modulate induced type I IFN responses in innate immune cells by degradation of STING [Research]
The cyclic dinucleotides, GMP–AMP (cGAMP) and c-di-AMP [bis-(3',5')-cyclic dimeric AMP], are potent type I IFN inducers via STING-TBK1-IRF3 cascade. They are promising adjuvants that promote antigen-specific humoral and cellular immune responses in different preclinical models; however, an optimal outcome of vaccination depends on a balanced immune activation. Here, we characterize the process of IFN-β induction by c-di-AMP and cGAMP in an in vitro model on the basis of primary mouse dendritic cells. Results obtained show decreased IFN-β production upon prolonged cell stimulation. We demonstrate that this e...
Source: FASEB Journal - June 29, 2017 Category: Biology Authors: Rueckert, C., Rand, U., Roy, U., Kasmapour, B., Strowig, T., Guzman, C. A. Tags: Research Source Type: research
Maternofetal transport of vitamin B12: role of TCblR/CD320 and megalin [Research]
Vitamin B12 deficiency causes megaloblastic anemia and neurologic disorder in humans. Gene defects of transcobalamin (TC) and the transcobalamin receptor (TCblR), needed for cellular uptake of the TC-bound B12, do not confer embryonic lethality. TC deficiency can produce the hematologic and neurologic complications after birth, whereas TCblR/CD320 gene defects appear to produce mild metabolic changes. Alternate maternofetal transport mechanisms appear to provide adequate B12 to the fetus. To understand this mechanism, we evaluated the role of TC, TCblR/CD320, and megalin in maternofetal transport of B12 in a TCblR/CD320-kn...
Source: FASEB Journal - June 29, 2017 Category: Biology Authors: Arora, K., Sequeira, J. M., Quadros, E. V. Tags: Research Source Type: research
Epithelial chemokine CXCL14 synergizes with CXCL12 via allosteric modulation of CXCR4 [Research]
The chemokine receptor, CXC chemokine receptor 4 (CXCR4), is selective for CXC chemokine ligand 12 (CXCL12), is broadly expressed in blood and tissue cells, and is essential during embryogenesis and hematopoiesis. CXCL14 is a homeostatic chemokine with unknown receptor selectivity and preferential expression in peripheral tissues. Here, we demonstrate that CXCL14 synergized with CXCL12 in the induction of chemokine responses in primary human lymphoid cells and cell lines that express CXCR4. Combining subactive concentrations of CXCL12 with 100–300 nM CXCL14 resulted in chemotaxis responses that exceeded maximal respo...
Source: FASEB Journal - June 29, 2017 Category: Biology Authors: Collins, P. J., McCully, M. L., Martinez-Munoz, L., Santiago, C., Wheeldon, J., Caucheteux, S., Thelen, S., Cecchinato, V., Laufer, J. M., Purvanov, V., Monneau, Y. R., Lortat-Jacob, H., Legler, D. F., Uguccioni, M., Thelen, M., Piguet, V., Mellado, M., M Tags: Research Source Type: research
Macrophages utilize the mitochondrial calcium uniporter for profibrotic polarization [Research]
Fibrosis in multiple organs, including the liver, kidney, and lung, often occurs secondary to environmental exposure. Asbestos exposure is one important environmental cause of lung fibrosis. The mechanisms that mediate fibrosis is not fully understood, although mitochondrial oxidative stress in alveolar macrophages is critical for fibrosis development. Mitochondrial Ca2+ levels can be associated with production of reactive oxygen species. Here, we show that patients with asbestosis have higher levels of mitochondrial Ca2+ compared with normal patients. The mitochondrial calcium uniporter (MCU) is a highly selective ion cha...
Source: FASEB Journal - June 29, 2017 Category: Biology Authors: Gu, L., Larson-Casey, J. L., Carter, A. B. Tags: Research Source Type: research
Biophysical characterization of the Varroa destructor NaV1 sodium channel and its affinity for {tau}-fluvalinate insecticide [Research]
The decline of the western honeybee (Apis mellifera) has been reported to be due to parasitism by Varroa destructor mites and to colony collapse disorder in which these mites may be involved. In-hive chemicals such as -fluvalinate are being used to control V. destructor populations. This approach may lead to the chronic exposure of bees to this liposoluble chemical, which tends to accumulate in hives. We cloned a variant of the V. destructor voltage-dependent sodium (VdNaV1) channel and studied its biophysical characteristics and sensitivity to -fluvalinate using the Xenopus oocyte expression system and the 2-microelectrod...
Source: FASEB Journal - June 29, 2017 Category: Biology Authors: Gosselin-Badaroudine, P., Chahine, M. Tags: Research Source Type: research
