Chronic ethanol exposure closes the door to vitamin C in pancreatic acinar cells. Focus on "Uptake of ascorbic acid by pancreatic acinar cells is negatively impacted by chronic alcohol exposure"
(Source: AJP: Cell Physiology)
Source: AJP: Cell Physiology - July 12, 2016 Category: Cytology Authors: Ticho, A. L., Alrefai, W. A. Tags: EDITORIAL FOCUS Source Type: research
Fluid transport by the cornea endothelium is dependent on buffering lactic acid efflux
Maintenance of corneal hydration is dependent on the active transport properties of the corneal endothelium. We tested the hypothesis that lactic acid efflux, facilitated by buffering, is a component of the endothelial fluid pump. Rabbit corneas were perfused with bicarbonate-rich (BR) or bicarbonate-free (BF) Ringer of varying buffering power, while corneal thickness was measured. Perfusate was collected and analyzed for lactate efflux. In BF with no added HEPES, the maximal corneal swelling rate was 30.0 ± 4.1 μm/h compared with 5.2 ± 0.9 μm/h in BR. Corneal swelling decreased directly with [HEPES], s...
Source: AJP: Cell Physiology - July 4, 2016 Category: Cytology Authors: Li, S., Kim, E., Bonanno, J. A. Tags: ARTICLES Source Type: research
Valproic acid attenuates skeletal muscle wasting by inhibiting C/EBP{beta}-regulated atrogin1 expression in cancer cachexia
Muscle wasting is the hallmark of cancer cachexia and is associated with poor quality of life and increased mortality. Valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, has important biological effects in the treatment of muscular dystrophy. To verify whether VPA could ameliorate muscle wasting induced by cancer cachexia, we explored the role of VPA in two cancer cachectic mouse models [induced by colon-26 (C26) adenocarcinoma or Lewis lung carcinoma (LLC)] and atrophied C2C12 myotubes [induced by C26 cell conditioned medium (CCM) or LLC cell conditioned medium (LCM)]. Our data demonstrated that treatment with V...
Source: AJP: Cell Physiology - July 4, 2016 Category: Cytology Authors: Sun, R., Zhang, S., Hu, W., Lu, X., Lou, N., Yang, Z., Chen, S., Zhang, X., Yang, H. Tags: CALL FOR PAPERS Source Type: research
NLRP3 inflammasome signaling is activated by low-level lysosome disruption but inhibited by extensive lysosome disruption: roles for K+ efflux and Ca2+ influx
Nucleotide-binding domain, leucine-rich-repeat-containing family, pyrin domain-containing 3 (NLRP3) is a cytosolic protein that nucleates assembly of inflammasome signaling platforms, which facilitate caspase-1-mediated IL-1β release and other inflammatory responses in myeloid leukocytes. NLRP3 inflammasomes are assembled in response to multiple pathogen- or environmental stress-induced changes in basic cell physiology, including the destabilization of lysosome integrity and activation of K+-permeable channels/transporters in the plasma membrane (PM). However, the quantitative relationships between lysosome membrane p...
Source: AJP: Cell Physiology - July 4, 2016 Category: Cytology Authors: Katsnelson, M. A., Lozada-Soto, K. M., Russo, H. M., Miller, B. A., Dubyak, G. R. Tags: CALL FOR PAPERS Source Type: research
Dousing fire with gasoline: interplay between lysosome damage and the NLRP3 inflammasome. Focus on "NLRP3 inflammasome signaling is activated by low-level lysosome disruption but inhibited by extensive lysosome disruption: roles for K+ efflux and Ca2+ influx"
(Source: AJP: Cell Physiology)
Source: AJP: Cell Physiology - July 4, 2016 Category: Cytology Authors: Schilling, J. D. Tags: EDITORIAL FOCUS Source Type: research
The mitochondrial Ca2+ uniporter: regulation by auxiliary subunits and signal transduction pathways
Mitochondrial Ca2+ homeostasis, the Ca2+ influx-efflux balance, is responsible for the control of numerous cellular functions, including energy metabolism, generation of reactive oxygen species, spatiotemporal dynamics of Ca2+ signaling, and cell growth and death. Recent discovery of the molecular identity of the mitochondrial Ca2+ uniporter (MCU) provides new possibilities for application of genetic approaches to study the mitochondrial Ca2+ influx mechanism in various cell types and tissues. In addition, the subsequent discovery of various auxiliary subunits associated with MCU suggests that mitochondrial Ca2+ uptake is ...
Source: AJP: Cell Physiology - July 4, 2016 Category: Cytology Authors: Jhun, B. S., Mishra, J., Monaco, S., Fu, D., Jiang, W., Sheu, S.-S., O-Uchi, J. Tags: 2015 NEW INVESTIGATOR AWARD Source Type: research
With no lysine L-WNK1 isoforms are negative regulators of the K+-Cl- cotransporters
The K+-Cl– cotransporters (KCC1-KCC4) encompass a branch of the SLC12 family of electroneutral cation-coupled chloride cotransporters that translocate ions out of the cell to regulate various factors, including cell volume and intracellular chloride concentration, among others. L-WNK1 is an ubiquitously expressed kinase that is activated in response to osmotic stress and intracellular chloride depletion, and it is implicated in two distinct hereditary syndromes: the renal disease pseudohypoaldosteronism type II (PHAII) and the neurological disease hereditary sensory neuropathy 2 (HSN2). The effect of L-WNK1 on KCC ac...
Source: AJP: Cell Physiology - June 30, 2016 Category: Cytology Authors: Mercado, A., de los Heros, P., Melo, Z., Chavez-Canales, M., Murillo-de-Ozores, A. R., Moreno, E., Bazua-Valenti, S., Vazquez, N., Hadchouel, J., Gamba, G. Tags: ARTICLES Source Type: research
The Ste20 kinases SPAK and OSR1 travel between cells through exosomes
Proteomics studies have identified Ste20-related proline/alanine-rich kinase (SPAK) and oxidative stress response 1 (OSR1) in exosomes isolated from body fluids such as blood, saliva, and urine. Because proteomics studies likely overestimate the number of exosome proteins, we sought to confirm and extend this observation using traditional biochemical and cell biology methods. We utilized HEK293 cells in culture to verify the packaging of these Ste20 kinases in exosomes. Using a series of centrifugation and filtration steps of conditioned culture medium isolated from HEK293 cells, we isolated nanovesicles in the range of 40...
Source: AJP: Cell Physiology - June 30, 2016 Category: Cytology Authors: Koumangoye, R., Delpire, E. Tags: ARTICLES Source Type: research
When phosphorylated at Thr148, the {beta}2-subunit of AMP-activated kinase does not associate with glycogen in skeletal muscle
The 5'-AMP-activated protein kinase (AMPK), a heterotrimeric complex that functions as an intracellular fuel sensor that affects metabolism, is activated in skeletal muscle in response to exercise and utilization of stored energy. The diffusibility properties of α- and β-AMPK were examined in isolated skeletal muscle fiber segments dissected from rat fast-twitch extensor digitorum longus and oxidative soleus muscles from which the surface membranes were removed by mechanical dissection. After the muscle segments were washed for 1 and 10 min, ~60% and 75%, respectively, of the total AMPK pools were found in the d...
Source: AJP: Cell Physiology - June 30, 2016 Category: Cytology Authors: Xu, H., Frankenberg, N. T., Lamb, G. D., Gooley, P. R., Stapleton, D. I., Murphy, R. M. Tags: CALL FOR PAPERS Source Type: research
Calpain-2 activates Akt via TGF-{beta}1-mTORC2 pathway in pulmonary artery smooth muscle cells
Calpain is a family of calcium-dependent nonlysosomal neutral cysteine endopeptidases. Akt is a serine/threonine kinase that belongs to AGC kinases and plays important roles in cell survival, growth, proliferation, angiogenesis, and cell metabolism. Both calpain and Akt are the downstream signaling molecules of platelet-derived growth factor (PDGF) and mediate PDGF-induced collagen synthesis and proliferation of pulmonary artery smooth muscle cells (PASMCs) in pulmonary vascular remodeling. We found that inhibitions of calpain-2 by using calpain inhibitor MDL28170 and calpain-2 small interfering RNA attenuated Akt phosphor...
Source: AJP: Cell Physiology - June 30, 2016 Category: Cytology Authors: Abeyrathna, P., Kovacs, L., Han, W., Su, Y. Tags: CALL FOR PAPERS Source Type: research
Regulation of membrane KCNQ1/KCNE1 channel density by sphingomyelin synthase 1
Sphingomyelin synthase (SMS) catalyzes the conversion of phosphatidylcholine and ceramide to sphingomyelin and diacylglycerol. We previously showed that SMS1 deficiency leads to a reduction in expression of the K+ channel KCNQ1 in the inner ear (Lu MH, Takemoto M, Watanabe K, Luo H, Nishimura M, Yano M, Tomimoto H, Okazaki T, Oike Y, and Song WJ. J Physiol 590: 4029–4044, 2012), causing hearing loss. However, it remains unknown whether this change in expression is attributable to a cellular process or a systemic effect in the knockout animal. Here, we examined whether manipulation of SMS1 activity affects KCNQ1/KCNE1...
Source: AJP: Cell Physiology - June 30, 2016 Category: Cytology Authors: Wu, M., Takemoto, M., Taniguchi, M., Takumi, T., Okazaki, T., Song, W.-J. Tags: CALL FOR PAPERS Source Type: research
Tumor cell intravasation
The process of entering the bloodstream, intravasation, is a necessary step in the development of distant metastases. The focus of this review is on the pathways and molecules that have been identified as being important based on current in vitro and in vivo assays for intravasation. Properties of the vasculature which are important for intravasation include microvessel density and also diameter of the vasculature, with increased intravasation correlating with increased vessel diameter in some tumors. TGFB signaling can enhance intravasation at least in part through induction of EMT, and we discuss other TGFB target genes ...
Source: AJP: Cell Physiology - June 30, 2016 Category: Cytology Authors: Chiang, S. P. H., Cabrera, R. M., Segall, J. E. Tags: THEMES Source Type: research
Chronology of UPR activation in skeletal muscle adaptations to chronic contractile activity
The mitochondrial and endoplasmic reticulum unfolded protein responses (UPRmt and UPRER) are important for cellular homeostasis during stimulus-induced increases in protein synthesis. Exercise triggers the synthesis of mitochondrial proteins, regulated in part by peroxisome proliferator activator receptor- coactivator 1α (PGC-1α). To investigate the role of the UPR in exercise-induced adaptations, we subjected rats to 3 h of chronic contractile activity (CCA) for 1, 2, 3, 5, or 7 days followed by 3 h of recovery. Mitochondrial biogenesis signaling, through PGC-1α mRNA, increased 14-fold after 1 day of CCA...
Source: AJP: Cell Physiology - June 14, 2016 Category: Cytology Authors: Memme, J. M., Oliveira, A. N., Hood, D. A. Tags: ARTICLES Source Type: research
Lithocholic acid attenuates cAMP-dependent Cl- secretion in human colonic epithelial T84 cells
In this study, we explored the effect of LCA on the action of other secretagogues in T84 cells. While LCA (50 μM, 15 min) drastically (>90%) inhibited FSK-stimulated short-circuit current (Isc), it did not alter carbachol-stimulated Isc. LCA did not alter basal Isc, transepithelial resistance, cell viability, or cytotoxicity. LCA's inhibitory effect was dose dependent, acted faster from the apical membrane, rapid, and not immediately reversible. LCA also prevented the Isc stimulated by the cAMP-dependent secretagogues 8-bromo-cAMP, lubiprostone, or chenodeoxycholic acid (CDCA). The LCA inhibitory effect was BA specif...
Source: AJP: Cell Physiology - June 14, 2016 Category: Cytology Authors: Ao, M., Domingue, J. C., Khan, N., Javed, F., Osmani, K., Sarathy, J., Rao, M. C. Tags: ARTICLES Source Type: research
Local coupling of TRPC6 to ANO1/TMEM16A channels in smooth muscle cells amplifies vasoconstriction in cerebral arteries
Anoctamin-1 [ANO1, also known as transmembrane protein 16A (TMEM16A)] is a Ca2+-activated Cl– channel expressed in arterial myocytes that regulates membrane potential and contractility. Signaling mechanisms that control ANO1 activity in arterial myocytes are poorly understood. In cerebral artery myocytes, ANO1 channels are activated by local Ca2+ signals generated by plasma membrane nonselective cation channels, but the molecular identity of these proteins is unclear. Arterial myocytes express several different nonselective cation channels, including multiple members of the transient receptor potential receptor (TRP)...
Source: AJP: Cell Physiology - June 14, 2016 Category: Cytology Authors: Wang, Q., Leo, M. D., Narayanan, D., Kuruvilla, K. P., Jaggar, J. H. Tags: CALL FOR PAPERS Source Type: research
