The ubiquitin proteasome system in atrophying skeletal muscle: roles and regulation
Muscle atrophy complicates many diseases as well as aging, and its presence predicts both decreased quality of life and survival. Much work has been conducted to define the molecular mechanisms involved in maintaining protein homeostasis in muscle. To date, the ubiquitin proteasome system (UPS) has been shown to play an important role in mediating muscle wasting. In this review, we have collated the enzymes in the UPS whose roles in muscle wasting have been confirmed through loss-of-function studies. We have integrated information on their mechanisms of action to create a model of how they work together to produce muscle a...
Source: AJP: Cell Physiology - August 31, 2016 Category: Cytology Authors: Bilodeau, P. A., Coyne, E. S., Wing, S. S. Tags: THEMES Source Type: research
Biotin deficiency enhances the inflammatory response of human dendritic cells
The water-soluble biotin (vitamin B7) is indispensable for normal human health. The vitamin acts as a cofactor for five carboxylases that are critical for fatty acid, glucose, and amino acid metabolism. Biotin deficiency is associated with various diseases, and mice deficient in this vitamin display enhanced inflammation. Previous studies have shown that biotin affects the functions of adaptive immune T and NK cells, but its effect(s) on innate immune cells is not known. Because of that and because vitamins such as vitamins A and D have a profound effect on dendritic cell (DC) function, we investigated the effect of biotin...
Source: AJP: Cell Physiology - August 31, 2016 Category: Cytology Authors: Agrawal, S., Agrawal, A., Said, H. M. Tags: ARTICLES Source Type: research
Molecular mechanisms of the angiogenic effects of low-energy shock wave therapy: roles of mechanotransduction
In this study, we thus examined the effects of SW irradiation on intracellular signaling pathways in vitro. Cultured human umbilical vein endothelial cells (HUVECs) were treated with 800 shots of low-energy SW (1 Hz at an energy level of 0.03 mJ/mm2). The SW therapy significantly upregulated mRNA expression and protein levels of vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS). The SW therapy also enhanced phosphorylation of extracellular signal-regulated kinase 1/2 (Erk1/2) and Akt. Furthermore, the SW therapy enhanced phosphorylation of caveolin-1 and the expression of HUTS-4 that re...
Source: AJP: Cell Physiology - August 31, 2016 Category: Cytology Authors: Hatanaka, K., Ito, K., Shindo, T., Kagaya, Y., Ogata, T., Eguchi, K., Kurosawa, R., Shimokawa, H. Tags: CALL FOR PAPERS Source Type: research
Active vacuolar H+ ATPase and functional cycle of Rab5 are required for the vacuolation defect triggered by PtdIns(3,5)P2 loss under PIKfyve or Vps34 deficiency
We report here that inhibition of V-ATPase with bafilomycin A1 as well as inactivation of the GTP-GDP cycle of Rab5a GTPase phenotypically rescued or completely precluded the cytoplasmic vacuolization despite the continued presence of inactivated PIKfyve or Vps34. Bafilomycin A1 also restored the aberrant EEA1-positive endosomes, enlarged upon short PIKfyve inhibition with YM201636. Together, our work identifies for the first time that factors such as active V-ATPase or functional Rab5a cycle are acting coincidentally with the PtdIns(3,5)P2 reduction in triggering formation of aberrant cytoplasmic vacuoles under PIKfyve or...
Source: AJP: Cell Physiology - August 31, 2016 Category: Cytology Authors: Compton, L. M., Ikonomov, O. C., Sbrissa, D., Garg, P., Shisheva, A. Tags: CALL FOR PAPERS Source Type: research
New pieces in the complex puzzle of aberrant vacuolation. Focus on "Active vacuolar H+ ATPase and functional cycle of Rab5 are required for the vacuolation defect triggered by PtdIns(3,5)P2 loss under PIKfyve or Vps34 deficiency"
(Source: AJP: Cell Physiology)
Source: AJP: Cell Physiology - August 31, 2016 Category: Cytology Authors: Saveanu, L., Lotersztajn, S. Tags: EDITORIAL FOCUS Source Type: research
Fine-tuning autophagy: from transcriptional to posttranslational regulation
Macroautophagy (hereafter called autophagy) is a vacuolar lysosomal pathway for degradation of intracellular material in eukaryotic cells. Autophagy plays crucial roles in tissue homeostasis, in adaptation to stress situations, and in immune and inflammatory responses. Alteration of autophagy is associated with cancer, diabetes and obesity, cardiovascular disease, neurodegenerative disease, autoimmune disease, infection, and chronic inflammatory disease. Autophagy is controlled by autophagy-related (ATG) proteins that act in a coordinated manner to build up the initial autophagic vacuole named the autophagosome. It is now ...
Source: AJP: Cell Physiology - August 31, 2016 Category: Cytology Authors: Botti-Millet, J., Nascimbeni, A. C., Dupont, N., Morel, E., Codogno, P. Tags: THEMES Source Type: research
Soluble adenylyl cyclase is an acid-base sensor in epithelial base-secreting cells
This study demonstrates that sAC is a necessary and sufficient sensor of extracellular alkalosis in ray gill base-secreting cells. In addition, this study indicates that different sources of cAMP differentially modulate cell biology. (Source: AJP: Cell Physiology)
Source: AJP: Cell Physiology - August 8, 2016 Category: Cytology Authors: Roa, J. N., Tresguerres, M. Tags: ARTICLES Source Type: research
Chamber-specific differences in human cardiac fibroblast proliferation and responsiveness toward simvastatin
Fibroblasts, the most abundant cells in the heart, contribute to cardiac fibrosis, the substrate for the development of arrythmogenesis, and therefore are potential targets for preventing arrhythmic cardiac remodeling. A chamber-specific difference in the responsiveness of fibroblasts from the atria and ventricles toward cytokine and growth factors has been described in animal models, but it is unclear whether similar differences exist in human cardiac fibroblasts (HCFs) and whether drugs affect their proliferation differentially. Using cardiac fibroblasts from humans, differences between atrial and ventricular fibroblasts...
Source: AJP: Cell Physiology - August 8, 2016 Category: Cytology Authors: Rizvi, F., DeFranco, A., Siddiqui, R., Negmadjanov, U., Emelyanova, L., Holmuhamedov, A., Ross, G., Shi, Y., Holmuhamedov, E., Kress, D., Tajik, A. J., Jahangir, A. Tags: ARTICLES Source Type: research
Human adipocytes from the subcutaneous superficial layer have greater adipogenic potential and lower PPAR-{gamma} DNA methylation levels than deep layer adipocytes
Human subcutaneous fat tissue consists of two layers, superficial adipose tissue (SAT) and deep adipose tissue (DAT). Some recent reports suggest that a disproportionate accumulation of DAT is related to obesity-associated metabolic complications. However, the differences in adipocyte function between SAT and DAT are unclear. To clarify the differences in human adipocyte characteristics between SAT and DAT, human ceiling culture-derived proliferative adipocytes (ccdPAs) were primary cultured from SAT and DAT of three lean female patients. Differences in adipogenic differentiation potential and sensitivity to exogenous adip...
Source: AJP: Cell Physiology - August 8, 2016 Category: Cytology Authors: Kosaka, K., Kubota, Y., Adachi, N., Akita, S., Sasahara, Y., Kira, T., Kuroda, M., Mitsukawa, N., Bujo, H., Satoh, K. Tags: CALL FOR PAPERS Source Type: research
Green tea (-)-epigallocatechin gallate inhibits the growth of human villous trophoblasts via the ERK, p38, AMP-activated protein kinase, and protein kinase B pathways
This study investigated the pathways involved in EGCG modulation of trophoblast mitogenesis. EGCG inhibited trophoblast proliferation in a dose-dependent and time-dependent manner, as indicated by the number of cells and incorporation of bromodeoxyuridine (BrdU). EGCG was more effective than other green tea catechins in inhibiting cell growth. EGCG also increased the phosphorylation of the MAPK pathway proteins, ERK1/2, and p38, but not JNK. Furthermore, EGCG had no effects on the total amounts of ERK1/2, p38 MAPK, and JNK proteins. This suggests that EGCG selectively affects particular MAPK subfamilies. Pretreatment with ...
Source: AJP: Cell Physiology - August 8, 2016 Category: Cytology Authors: Shih, L.-J., Chen, T.-F., Lin, C.-K., Liu, H.-S., Kao, Y.-H. Tags: CALL FOR PAPERS Source Type: research
Role of scleraxis in mechanical stretch-mediated regulation of cardiac myofibroblast phenotype
The phenotype conversion of fibroblasts to myofibroblasts plays a key role in the pathogenesis of cardiac fibrosis. Numerous triggers of this conversion process have been identified, including plating of cells on solid substrates, cytokines such as transforming growth factor-β, and mechanical stretch; however, the underlying mechanisms remain incompletely defined. Recent studies from our laboratory revealed that the transcription factor scleraxis is a key regulator of cardiac fibroblast phenotype and extracellular matrix expression. Here we report that mechanical stretch induces type I collagen expression and morpholo...
Source: AJP: Cell Physiology - August 8, 2016 Category: Cytology Authors: Roche, P. L., Nagalingam, R. S., Bagchi, R. A., Aroutiounova, N., Belisle, B. M. J., Wigle, J. T., Czubryt, M. P. Tags: CALL FOR PAPERS Source Type: research
Ubiquitin-dependent and independent roles of SUMO in proteostasis
Cellular proteomes are continuously undergoing alterations as a result of new production of proteins, protein folding, and degradation of proteins. The proper equilibrium of these processes is known as proteostasis, implying that proteomes are in homeostasis. Stress conditions can affect proteostasis due to the accumulation of misfolded proteins as a result of overloading the degradation machinery. Proteostasis is affected in neurodegenerative diseases like Alzheimer's disease, Parkinson's disease, and multiple polyglutamine disorders including Huntington's disease. Owing to a lack of proteostasis, neuronal cells build up ...
Source: AJP: Cell Physiology - August 8, 2016 Category: Cytology Authors: Liebelt, F., Vertegaal, A. C. O. Tags: The Control of the Proteostasis Network in Health and Diseases THEMES Source Type: research
SarcOptiM for ImageJ: high-frequency online sarcomere length computing on stimulated cardiomyocytes
In conclusion, SarcOptiM is a free and validated user-friendly tool for studying cardiomyocyte contraction in all species, including human. (Source: AJP: Cell Physiology)
Source: AJP: Cell Physiology - July 31, 2016 Category: Cytology Authors: Pasqualin, C., Gannier, F., Yu, A., Malecot, C. O., Bredeloux, P., Maupoil, V. Tags: METHODS IN CELL PHYSIOLOGY Source Type: research
Reduced ATGL-mediated lipolysis attenuates {beta}-adrenergic-induced AMPK signaling, but not the induction of PKA-targeted genes, in adipocytes and adipose tissue
5'-AMP-activated protein kinase (AMPK) is activated as a consequence of lipolysis and has been shown to play a role in regulation of adipose tissue mitochondrial content. Conversely, the inhibition of lipolysis has been reported to potentiate the induction of protein kinase A (PKA)-targeted genes involved in the regulation of oxidative metabolism. The purpose of the current study was to address these apparent discrepancies and to more fully examine the relationship between lipolysis, AMPK, and the β-adrenergic-mediated regulation of gene expression. In 3T3-L1 adipocytes, the adipose tissue triglyceride lipase (ATGL) i...
Source: AJP: Cell Physiology - July 31, 2016 Category: Cytology Authors: MacPherson, R. E. K., Dragos, S. M., Ramos, S., Sutton, C., Frendo-Cumbo, S., Castellani, L., Watt, M. J., Perry, C. G. R., Mutch, D. M., Wright, D. C. Tags: ARTICLES Source Type: research
Polyunsaturated fatty acids inhibit Kv1.4 by interacting with positively charged extracellular pore residues
Polyunsaturated fatty acids (PUFAs) modulate voltage-gated K+ channel inactivation by an unknown site and mechanism. The effects of -6 and -3 PUFAs were investigated on the heterologously expressed Kv1.4 channel. PUFAs inhibited wild-type Kv1.4 during repetitive pulsing as a result of slowing of recovery from inactivation. In a mutant Kv1.4 channel lacking N-type inactivation, PUFAs reversibly enhanced C-type inactivation (Kd, 15–43 μM). C-type inactivation was affected by extracellular H+ and K+ as well as PUFAs and there was an interaction among the three: the effect of PUFAs was reversed during acidosis and abo...
Source: AJP: Cell Physiology - July 31, 2016 Category: Cytology Authors: Farag, N. E., Jeong, D., Claydon, T., Warwicker, J., Boyett, M. R. Tags: ARTICLES Source Type: research
