bluuebunny/crossref_metadata_2025_split huggingface dataset:
Satellite cells regulate the skeletal muscle environment by inhibiting fibroblast function
Authors: Fry Christopher S , Lee Jonah D , Jackson Janna R , Kirby Tyler J , Dupont‐Versteegden Esther E , McCarthy John J , Peterson Charlotte A 
Published: June 2021

Interaction between satellite cells and the skeletal muscle extracellular matrix (ECM) has been demonstrated, but a role for satellite cells in regulating the ECM during hypertrophy has not been defined. We utilized mouse primary myoblasts and fibroblasts in co‐culture in addition to a genetically modified mouse model (Pax7‐DTA) to investigate the role of satellite cells in the regulation of muscle ECM. The Pax7‐DTA mouse allows for the conditional depletion of satellite cells in adult muscle following tamoxifen administration. Vehicle/tamoxifen treated animals were randomized to sham or synergist ablation surgery, leading to overload of the plantaris muscle for 1 and 8 weeks. Microarray analysis after 1 week of surgery showed the loss of satellite cells was associated with increased expression of numerous collagens and ECM structural genes. Depletion of satellite cells also led to attenuated hypertrophy and fibrosis of the plantaris with increases in both ECM deposition and fibroblast number following 8 weeks of overload. Co‐culturing mouse myoblasts with fibroblasts led to decreased mRNA expression of Col Ia2, IIIa1, VIa2 and Fibronectin compared to fibroblasts cocultured with fibroblasts, suggesting a paracrine role of myoblasts that inhibits fibroblast ECM production. We conclude that a novel function of satellite cells both at rest and during hypertrophy is to regulate muscle fibroblasts and the ECM.Funding: NIAMS R01AR060701, R21AG34453 and the Jeane B. Kempner Postdoctoral Award.
Brain‐derived neurotrophic factor augments the contraction of intestinal longitudinal muscle strips induced by Carbachol
Authors: Alqudah Mohammad , Mahavadi Sunila , Srinivasa Karnam M. , Grider Jack 
Published: June 2021

BackgroundWe have demonstrated that intestinal longitudinal smooth muscle cells synthesize and secrete brain derived neurotrophic factor (BDNF) in response to neuropeptide transmitters. But the function of this BDNF in the gastrointestinal tract is undetermined.Aimto test the effect of BDNF on agonist‐induced contraction in intestinal longitudinal smooth muscle.Material and methodRabbit longitudinal muscle strips were prepared from the intestine. The contraction of the muscle strips was recorded in response to substance P 10–6M (SP 10–6) and Carbachol 10–5M (CCh 10–5). Muscle strips were preincubated with 10 nM exogenous BDNF and the changes in SP/CCh‐induced contraction were examined. A Trk antagonist and two Trk B specific agonists were used to investigate the role of the Trk B receptor in the effect of BDNF on contraction.ResultsBDNF significantly enhanced the contraction of longitudinal smooth muscle induced by CCh 10–5. However, contraction induced by SP 10–6 was not affected by pretreatment with BDNF. The pan Trk receptor inhibitor (K252a) inhibited the effect of BDNF on CCh‐induced contraction. Moreover, two Trk B agonists (LM 22A4 & 7, 8‐dihydroxyflavone) augmented the CCh‐induced contraction of the longitudinal muscle strips.ConclusionBDNF enhances the cholinergic‐induced longitudinal muscle contraction through the activation of its cognate Trk B receptor.
Dopamine enhances gastric motility through D1 dopaminergic receptors on cholinergic neurons in the myenteric plexus of rats
Authors: Song Jin , Zheng Lifei , Xu Jingdong , Zhu Jinxia 
Published: June 2021

ObjectivesInvestigate the effect of dopamine on the gastric motility and the underlying mechanism.MethodsImmunofluorescence and gastric motility recording by organ bath study.ResultThe immunoreactivities of D1 and D2 were distributed in the choline acetyltransferase (ChAT)‐immunoreactive neurons in the myenteric plexus of rats. The gastric motility in vitro was enhanced from 8.2 to 10.8£g¡Ámin£©by DA in the concentrations of 1¡Á10–8mol/L (n=10, p<0.05). However, DA manifested inhibitory role at the higher concentrations of 3¡Á10–6mol/L. The excitatory effect of DA was mimicked by SKF‐38393, a selective agonist of D1‐like receptors in dose‐dependent manner, and blocked by neuronal sodium channel blocker, tetrodotoxin (TTX) in 1¡Á10–5mol/L and atropine (competitive nonselective antagonist of muscarinic acetylcholine receptors) in 1¡Á10–5mol/L (n=8, p<0.05). The selective D2‐like receptor antagonist sulpride and selective D2‐like agonist Quipirole did not affect both the excitatory and inhibitory effect of DA.ConclusionsThe present study demonstrates that dopamine is able to enhance gastric motility in lower concentration through D1 dopaminergic receptors activating acetylcholine release from myenteric nerve plexus. The higher dose of DA can inhibit gastric motility, but the mechanism needs to be further investigated.
Increased corticosterone levels contribute to glucose intolerance induced by the absence of melatonin
Authors: Rodrigues Sandra Campos , Pantaleão Lucas , Lellis‐Santos Camilo , Veras Katherine , Amaral Fernanda , Anhê Gabriel , Bordin Silvana 
Published: June 2021

Pinealectomized rats (PINX) become glucose intolerant and exhibit increased gluconeogenesis. Melatonin is known to reduce glucocorticoid (GC) secretion, but the role of GC on the glucose intolerance of PINX is not described. Here we evaluated the participation of GC in the glucose intolerance of PINX rats. Rats were subjected to pinealectomy or fictitious surgery (sham) and treated with RU486 [0,5mg/100g/5days] or vehicle 25 days after surgeries. After that, rats were subjected to glucose and pyruvate tolerance tests. Livers were used for assessment of insulin‐induced maximal AKT activation; plasma was collected for insulin and corticosterone. The experiments were conducted at the end of the light phase of the light/dark cycle. Corticosterone levels were 30% higher in PINX (p>;0.05), compared to sham. Glucose intolerance and upregulated gluconeogenesis found in PINX were reduced by 50% after treatment with RU486 (p>;0.05). Reduced insulin levels found in PINX rats were recovered by RU486. Concordantly, insulin‐induced AKT phosphorylation in PINX (that was decreased when compared to sham; p>;0.05) was also upregulated after treatment with RU486 by 40%. We concluded that glucose intolerance of PINX rats is characterized by hepatic insulin resistance and reduced insulin levels. These metabolic adaptations may be a result of increased corticosterone levels.Financial Support: FAPESP (2011/12329–1)
Changes in angiotensin II‐induced vasomotor function from newborn to senescence: correlation with expression of AT1 and AT2 receptors
Authors: Vamos Zoltan , Cseplo P , Batai Z , Torok O , Ivic I , Matics R , Hamar J , Koller A 
Published: June 2021

Angiotensin II (Ang II) via activating angiotensin type 1 receptors (AT1R) is a potent vasoconstrictor, whereas recent studies suggest a role for AT2R in the modulation of vasomotor tone (VT). There are few data, however regarding aging‐induced changes in Ang II‐induced VT. We hypothesized that from newborn to senescence age there are substantial changes in the Ang II‐induced VT, mediated by AT1R and/or AT2R.Changes in isometric force to Ang II of carotid arteries (CA) of newborn (8 days: 8d), young (2–9 months[m]: 2–9m), adult (12–20m) and senescence (20–30m) rats were measured with a wire myograph (DMT 610). To assess the role of AT2R, an AT1R blocker (losartan) was used. Expressions (exp.) of AT1R and AT2R of CA were determined by rt‐PCR.Ang II‐induced contractions increased from 8d to 6m (8d: 1.4±0.4, 1m: 2.3±0.2, 2m: 5.3±0.5, 6m: 5.9±0.4 mN), then decreased to the age of 30m (9m: 5.5±0.2, 12m: 5.2±0.5, 24 m: 4.8±0.2, 30m: 3.7±0.6mN,). In the presence of losartan, Ang II did not elicited significant changes VT in any age group. Exp. of AT1R correlated with functional data: increased from 8d to 12m (8d: 1±0, 6m: 12±3.5, 12m: 15±2.7 cpm), then decreased to the age of 30m (18m: 7.3±0.5, 30m: 2.4±0,8cpm). There were no differences in the exp. of AT2R form 8d to 30m.In conclusion, Ang II‐induced vasoconstriction via AT1R showed an inverse U‐shape as a function of age. The similar pattern in vascular AT1R exp. suggests genetic determination.Supported by HNSRF ‐ OTKA K71591 and T67984, AHA F. Aff., 0555897T, HSH 2010/2011 and SROP‐4.2.1/b‐10/2/KONV‐2010–0012, SROP‐4.2.2.A‐11/1/KONV‐2012–0024.
Administration of PNS on collagen level in tissue of lung fibrosis in mice
Authors: Xiaofang SUN , NIU Jianzaho , DUAN Fei , HUANG Chunfang , WANG Jifeng 
Published: June 2021

To study the administration PNS(Panax notoginsenosides) on collagen level in lung tissue for mice. One hundred and eighty C57BL/6 male mice were divided into six groups: sham group, model group, PNS high, medium and low dose group, prednisone group (n = 30). In addition to the sham group, the remaining mice received a single intratracheal instillation of bleomycin, sham group received a single intratracheal instillation with saline. Two days after modeling, starting administration of PNS, until the day before the animals were killed. Administration of PNS high, medium and low dose group were 120, 60, 30mg/kg/d respectively, administration of prednisone group was 0.56mg/kg, sham group, model group were given equal volume of saline. All the animals at 7, 14, 28 d were killed, lungs were taken for HE, Mallory staining, and determination of lung hydroxyproline content.RESULTSAdministration of PNS could reduce pulmonary fibrosis in mice as indicated by lower collagen content of lung tissue, reduce the proliferation of fibrous lung tissue.ConclutionAdministration of PNS can reduce pulmonary fibrosis in mice with less collagen content of lung tissue in mice. Supported by 111 project B07007
Pro‐inflammatory Role of Beta2‐Adrenoceptor Signaling in Human Airway Epithelial Cells in Response to IL‐13
Authors: Al‐Sawalha Nour Ahmad , Pokkunuri Indira , Bond Richard A. , Knoll Brian J. 
Published: June 2021

We have shown the role of β2‐adrenoceptor (β2AR) signaling in inducing mucin content and inflammation in murine model of asthma. Our objective was to study the role of β2AR signaling in chemokine production and expression of a major airway mucin coding gene, MUC5AC, in normal human bronchial epithelial cells (NHBECs) in response to IL‐13. NHBECs were grown at air‐liquid interface (ALI) on transwell filters in the presence of 3μM epinephrine. Chemokine levels in subnatants were measured by multiplex ELISA on day 5 ALI. MUC5AC expression and phospho‐ERK1/2 were assessed by qRT‐PCR and immunoblotting on day 14 ALI. IL‐13 induced the release of eotaxin‐2, CXCL‐1 and MCP‐1 (eosinophil, monocyte, dendritic and memory T‐cell chemoattractants respectively) by 6.8, 3.8 and 6.9 fold respectively. Treatment with βAR antagonist nadolol reduced the levels of these chemokines to baseline. Nadolol and ICI‐118,551 (a β2AR selective antagonist) blocked IL‐13 induced MUC5AC expression, while CGP‐20712A (a β1AR selective antagonist) did not. U0126 (a MEK‐1/2 inhibitor) and H89 (a PKA inhibitor) reduced IL‐13 induced MUC5AC expression, but only U0126 reduced phospho‐ERK1/2 levels. Our data provides a strong evidence of the pro‐inflammatory role of β2AR signaling in mediating IL‐13 effect on human airway epithelium, and that ERK‐1/2 and PKA are components of the required β2AR signaling pathways.Supported by NIH 1R01A179236 to RAB
Pregnane X Receptor Mediates Dyslipidemia Induced by the HIV Protease Inhibitor Amprenavir in Mice
Authors: Helsley Robert Nathaniel , Sui Yipeng , Ai Ni , Park Se‐Hyung , Welsh William J. , Zhou Changcheng 
Published: June 2021

HIV protease inhibitors have been used successfully in extending the lifespan of people infected with HIV. However, the mechanisms responsible for the increased risk of dyslipidemia and cardiovascular diseases associated with the use of protease inhibitors remain elusive. Several protease inhibitors have been implicated to activate the nuclear receptor pregnane X receptor (PXR), which acts as a xenobiotic sensor to regulate xenobiotic metabolism. We recently revealed PXR's pro‐atherogenic effects in animal models and found that chronic activation of PXR induces hyperlipidemia in wild‐type mice. In the present study, we found that a widely used HIV protease inhibitor, amprenavir, is a potent agonist of PXR. Amprenavir can induce expression of PXR target genes in human hepatoma HepaRG cells and intestinal LS180 cells. In silico ligand‐PXR docking studies combined with site‐direct mutagenesis identified several key residues within PXR's ligand binding pocket that constitute points of interaction with amprenavir. Lastly, amprenvir‐induced PXR activation significantly increased atherogenic lipoprotein LDL cholesterol levels in wild‐type mice, but had no effect in PXR knockout mice. These findings provide critical mechanistic insight for understanding the impact of protease inhibitors on cardiovascular disease and demonstrate a potential role of PXR in mediating adverse effects of HIV protease inhibitors in humans.This work is supported by NIH grants T32HL072743, P30HL101300, P20GM103527 and AHA grant 09SDG2150176.
Non‐Canonical Signaling by GPCR‐Arrestin‐Gβγ Ternary Complexes
Authors: Wehbi Vanessa L , Feinstein Timothy Nathan , Vilardaga Jean‐Pierre 
Published: June 2021

The classical model of arrestin‐mediated desensitization of GPCR is thought to be universal. In the current canonical model of GPCR signaling, arrestins terminate receptor signaling by impairing receptor–G protein coupling and promoting receptor internalization. However, this paradigm is incompatible with recent reports that the parathyroid hormone receptor (PTHR), a crucial GPCR for bone biology, sustains cAMP response for prolonged periods after ligand washout. Arrestins prolong GS‐mediated cAMP generation triggered by PTH, a process that correlates with the persistence of arrestin–PTHR complexes on endosomes, and which is thought to be associated with prolonged physiological calcemic and phosphate responses. This presents an inescapable paradox for the canonical model of arrestin‐mediated receptor–G protein decoupling. Here we show that PTHR forms a ternary complex that includes arrestin and Gβγ in response to PTH stimulation, which in turn increases the steady‐state levels of activated GS, leading to prolonged generation of cAMP. The non‐canonical signaling is not unique to the PTHR since we found that arrestin binding to the vasopressin V2 receptor prolonged cAMP production by vasopressin, which ultimately sustained water transport in kidney cells. This work provides a new model of GPCR signaling in which arrestins contribute to sustain agonist actions.Supported by the NIH award R01DK087688.
Cleavage of ROCK II: As a Common Phenomenon in Cell Death
Authors: Ozdemir Aysun , Ibisoglu Burcin , Simay Yaprak Dilber , Yaren Biljana Mitrovic , Ark Mustafa 
Published: June 2021

We have previously showed that caspase‐2 cleaved Rho kinase II (Rock II), one of the Rho kinase isoforms and produced a novel ~140 kDa fragment of the enzyme in HUVEC during ouabain‐induced apoptosis. In the current work we evaluated whether this cleavage is a common process in cell death. To test this hypothesis two different types of cancer cell lines HeLa and HepG2 were exposed to two different cardiac glycosides (1μM, 18h); ouabain, digoxin and a standard chemotherapeutic; paclitaxel (1 μM, 18 h) to induce cell death. After the induction, the effect of Rock inhibitor Y‐27632 (10 μM, 30 min before ouabain) and caspase inhibitors (50 μM, 2h before ouabain); caspase‐2 inhibitor z‐VDVAD‐fmk, caspase‐3 inhibitor Z‐DEVD‐fmk and pan caspase inhibitor z‐VAD‐fmk on cell death were examined. Treatment of ouabain, digoxin and paclitaxel resulted in concentration dependent cell‐substratum detachment and cell death. Neither Y‐27632 nor caspase inhibitors did not prevent drug‐induced cell detachment. Ouabain, digoxin and also paclitaxel treatment induced cleavage of Rock II in both HeLa and HepG2 cells. Although this cleavage was not inhibited by Y‐27632, all the caspase inhibitors prevented the proteolytic clevage of Rock II. It has been demonstrated that activation of caspase‐3 results in cleavage and activation of caspase‐2. Therefore our results point out that drug treatment induces activation of caspase‐3, which produces active caspase‐2 causing proteolytic cleavage of Rock II in cancer cells during cell death. As a conclusion, cleavage of Rock II by caspase‐2 is a common process in a cell‐type independent manner in cell death.This study is supported by TUBITAK in 110S426 project.
Effect of dietary calcium supplementation on store‐operated calcium entry in coronary smooth muscle cells from Ossabaw miniature swine with coronary artery disease
Authors: Martin John Robert , Lee McKenney Mikaela , Weaver Connie M. , Sturek Michael 
Published: June 2021

Coronary smooth muscle (CSM) cells of Ossabaw swine in the early stages of coronary artery disease have increased storeoperated calcium/cation entry (SOCE). Pigs (N=24) were fed for 6 months an atherogenic diet containing 0.5% Ca (control, C), or 2% Ca by supplementation with either calcium carbonate (high supplement, HS) or non‐fat milk (high dairy, HD) to determine effects on CSM SOCE. At euthanasia atherosclerosis was quantified with intravascular ultrasound and CSM cells were enzymatically isolated and loaded with fura‐2 to measure cytosolic Ca. The manganese (Mn) quench technique was used to assess SOCE after depletion of the sarcoplasmic reticulum (SR) with 5 mM caffeine. While maintaining SR depletion with 10 μM cyclopiazonic acid, the rate of quenching of fura‐2 fluorescence was measured as the percent change in pixel intensity/time (%Δ/min) to estimate SOCE. Mn quench from 64, 59, and 46 CSM (from 2 pigs/group) was in %Δ/min: C=−0.37±0.24, HD=0.04±0.01, HS=−0.42±0.51. These initial data suggest that Ca supplementation by skim milk prevented the increase in SOCE in CSM in atherosclerosis.(Support: NIH HL062552)
Alterations in the AKT/mTOR pathway in dystroglycanopathy muscle
Authors: Foltz Steven J , Beedle Aaron M 
Published: June 2021

Secondary dystroglycanopathies are a subset of muscular dystrophies caused by aberrant glycosylation of α‐Dystroglycan (DG). Hypoglycosylated αDG is unable to bind to its extracellular targets, disrupting a crucial link between the extracellular basement membrane and the intracellular cytoskeleton. FKTN, encoding fukutin, is one of several genes identified as causative for dystroglycanopathy. Similar to human patients, skeletal muscle from conditional fukutin KO mice shows a progressive dystrophic phenotype. The objective of our study is to characterize alterations in cellular signaling pathways in dystroglycanopathy disease using a conditional Fktn knockout mouse model. Using techniques to monitor gene expression, protein expression and protein phosphorylation, we find that there are alterations in multiple factors in the PI3K/AKT/mTOR signaling cascade in young Fktn KO mice. Furthermore, preliminary data suggest a differential response to pharmacological inhibition of this pathway between KO mice and age‐matched littermate controls. Our findings indicate that changes in the AKT/mTOR signaling pathway are present in young Fktn KO mice, but the precise role of AKT/mTOR signaling in dystroglycanopathy muscle requires further clarification.Research supported by the University of Georgia College of Pharmacy.
Nut intake and risk of metabolic syndrome
Authors: Jaceldo‐Siegl Karen , Oda Keiji , St John Claire , Sabaté Joan 
Published: June 2021

Studies of nut intake and metabolic syndrome (MetS) risk are sparse. We examined the relationship between nut consumption and MetS in the Adventist Health Study, a population with a wide range of nut intake ranging from never to daily. The analytic sample included 747 adults with complete demographic, diet, anthropometric, and clinical data. MetS was defined according to the AHA/NHLBI diagnostic criteria. Diet was assessed by a 204‐item FFQ (validated against 24‐hr diet recalls) including 8 items on nuts. Validity correlations were moderate for tree nuts and low to moderate for peanuts and peanut butter. Intake of tree nuts (T), peanuts + peanut butter (P), and total nuts (T+P) was quantified and categorized. Odds ratios with 95% CI were estimated using multivariable logistic regression. 35% of subjects had MetS. Total and tree nuts had an inverse association with MetS. Individuals with high total nuts intake (>;3 servings/week) had 34% less MetS than individuals with low intake (<1 serving/week) (OR=0.66, 95% CI: 0.43–0.99). Consumption of 1/day of tree nuts was associated with 20% lower odds of MetS (OR=0.80, 95% CI: 0.65–0.99). Consumption of peanuts was not related to MetS. In a population with high range of nut intake, consumption of total and tree nuts but not peanuts is associated with lower MetS. This association is independent of demographic, lifestyle and other dietary factors.Funding: NIH 1RO1 CA 94594 (data collection) and International Nut Council
Role of nitric oxide synthase on local sweat rate in older adults during intermittent exercise in the heat
Authors: Stapleton Jill , Carter Michael , Kenny Glen P. 
Published: June 2021

Studies suggest that nitric oxide (NO) has a role in sweating. Older adults have a lower production of and sensitivity to NO which may explain why older adults have lower local sweat rates (LSR) compared with their younger counterparts during exercise. We examined the role of NO synthase (NOS) on LSR during intermittent exercise in the heat. Ten young (Y) and ten older (O) participants completed 3 × 15 min of cycling (rate of metabolic heat production of 600 W) separated by 15 min recovery in the heat (35ºC, 30% RH). Intradermal microdialysis probes were inserted in the forearm and perfused with either 0.9% saline (CON) or 10 mM L‐NAME (a NOS inhibitor). LSR was measured directly over each membrane. LSR was similar between Y and O during the exercise bouts at the CON (average of the 3 exercise bouts: Y; 0.96 ± 0.20 vs. O; 0.87 ± 0.25 mg·min−1·cm−2 p=0.327) and the LNAME (Y: 0.74 ± 0.18 vs. O: 0.83 ± 0.27 mg·min−1·cm−2 p=0.327) sites. However, the relative contribution of NO to the sweating response was reduced in Y (CON: 0.96 ± 0.20 vs. L‐NAME: 0.74 ± 0.18 mg·min−1·cm−2, p=0.017), but not O (CON: 0.87 ± 0.25 vs. L‐NAME: 0.83 ± 0.27 mg·min−1·cm−2, p=0.965). We conclude that the exercise‐induced increase in sweating is influenced by NO in younger adults. However, it appears that the level of influence is blunted in older individuals during high intensity exercise in the heat.This research was funded by Natural Sciences and Engineering Research Council (RGPIN‐298159–2009, held by Dr. Kenny).