bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alterations in human neutrophil function by Bisphenol A
Authors: Balistrieri Angela , Meier Angela , Corriden Ross 
Published: June 2021

Bisphenol‐A is a synthetic organic compound frequently present in consumer plastics, including plastic‐lined cans, water bottles, toys, and teeth sutures. Previous studies have shown that BPA can produce adverse health effects that include defects in reproductive function and altered prenatal/childhood development. However, little is known regarding the effects of BPA on immune function. In this study, we assessed the effect of BPA on human neutrophils, a critical component of the innate immune system's defense against pathogens. We found that BPA induces a concentration‐dependent increase in reactive oxygen species generation by PMNs that is inhibited by the estrogen receptor β antagonist PHTPP and the NADPH oxidase inhibitor diphenyleneiodonium chloride. Furthermore, incubation with the membrane‐permeable calcium chelator BAPTA‐AM and/or removal of extracellular calcium inhibited BPA‐induced ROS production, indicating that the process is calcium dependent. Transwell chemotaxis assays revealed that BPA exposure reduces the chemotactic capacity of PMNs in a gradient of the bacterial cell wall component f‐Met‐Leu‐Phe, a potent chemoattractant. Exposure to BPA also inhibits the ability of neutrophils to kill methicillin‐resistant Staphylococcus aureus, a leading human pathogen. Our findings reveal that BPA alters the in vitro function of PMNs, including ROS production, chemotaxis and bacterial killing, and raise the possibility of altered innate immunity in vivo, especially in those with compromised immune function and who can be exposed to BPA in a wide variety of products.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Nrf2 Deletion is Associated with Impaired BKCa Channel Expression and Function in Rat Cerebral Arterial Muscle Cells
Authors: Gebremedhin Debebe , Harder David Rae , Lombard Julian H. 
Published: June 2021

The BKCa channel is ubiquitous in cerebral arterial muscle cells and other brain cell types and regulates cell excitability by sensing and reacting to changes in [Ca2+]. The BKCa channels are formed by tetramers of the pore‐forming α‐subunit and the accessary β1 subunit. The accessary β1 subunit unit is the sensor for changes in Ca2+ and voltage to regulate BKCa channel function. The BKCa channel is one of the downstream targets regulated by Nrf2 antioxidant defenses. We investigated the influence of deletion of Nrf2 on the expression and activities of BKCa single‐channel current in cerebral arterial muscle cells of Nrf2 wild type and knockout rats. In this study we found that the openings of a large conductance BKCa single‐channel current was markedly reduced in cerebral arterial muscle cells of Nrf2 knockout rats compared to those recorded from Nrf2 wild type rat cerebral arterial muscle cells at the same patch potential and symmetrical KCl (145 mM) recording solution. Nrf2 knockout also resulted in reduced expression of the proteins for both the pore forming BKCa channel α‐subunit and the accessary BKCa channel β‐subunit in rat cerebral arteries compared to cerebral arteries of Nrf2 wild type rats. Furthermore, knockout of Nrf2 significantly attenuated the ability of the Nrf2 activator sulforaphane (3 μM) to increase the openings of the BKCa single‐channel currents recorded from cell‐attached patches of Nrf2 knockout rat cerebral arterial muscle cells at a patch potential of 40 mV compared to those measured in Nrf2 wild type cerebral arterial muscle cells. These findings suggest that Nrf2 antioxidant defenses regulate BKCa channel expression and activity in rat cerebral arterial muscle cells and may influence the dynamics of the cerebral circulation under normal or oxidative stress conditions.Support or Funding InformationNIH #R01‐HL128242 and # R21‐OD018309) and NIH RO1 HL0338833.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Oxidative Stress‐Induced Changes in Ca2+ Sensitivity of Cardiomyocytes Do Not Recover
Authors: Piedrahita Tatiana Mejia , Osorio Sara , Han Young Soo , Diaz Rienzi , Sieck Gary 
Published: June 2021

Ca2+ sensitivity plays a critical role in regulating cardiac contraction, and pathophysiological changes in Ca2+ sensitivity of cardiac contraction may significantly impact cardiac function. For example, oxidative stress causes myocardial dysfunction, which is due in part to a decrease in Ca2+ sensitivity. Oxidative stress (e.g., elevated H2O2) underlies, at least in part, various conditions of cardiac dysfunction including ischemia‐reperfusion injury, heart failure, hypertension, and atherosclerosis. In cardiac muscle, Ca2+ sensitivity can be dynamically assessed using a phase loop plot of concurrently measured cytosolic Ca2+ concentration ([Ca2+]cyt) and sarcomere length shortening (Spurgeon et al J Physiol 447:83–102, 1992; Han et al Am J Physiol 298:890–897, 2010; Schaible et al Am J Physiol 310:1533–40, 2016). We hypothesized that oxidative stress reversibly reduces Ca2+ sensitivity of cardiomyocytes within minutes. Cardiomyocytes were isolated from adult rat hearts (Sprague Dawley) using a modified Langendorff system. Cardiomyocytes were loaded with Fura‐2 AM (Ca2+ fluorescent indicator; 1 mM) and electrically stimulated every 2 s. [Ca2+]cyt and sarcomere shortening responses to stimulation were simultaneously measured using an IonOptix System. After stabilization for 30 min at 35°C, cardiomyocytes were exposed to PSS for 10 min, then to H2O2 (200 μM) for 10 min and finally to either PSS washout or DTT (1 mM)‐induced reduction for 10 min. H2O2‐induced oxidative stress increased basal [Ca2+]cyt and the amplitude of the evoked [Ca2+]cyt response. H2O2‐induced oxidative stress also reduced the extent of sarcomere shortening and slowed the kinetics of shortening/relaxation. As a result, H2O2‐induced oxidative stress reduced Ca2+ sensitivity reflected by a rightward shift in the phase loop plots. Interestingly, with both PSS washout and DTT‐induced reduction Ca2+ sensitivity was further reduced. These results support the hypothesis that H2O2‐induced oxidative stress reduces Ca2+ sensitivity of cardiomyocytes, but this effect was not immediately reversed, but indeed worsened by PSS washout or by DTT‐induced reduction. Together, these results provide insight into the dynamic effects of oxidative stress on Ca2+ sensitivity of cardiomyocytes that may be reflected under pathological conditions.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Pannexin 1 channels in renin expressing cells regulate RAAS and blood pressure
Authors: DeLalio Leon J. , Keller TC Stevenson , Page Henry Askew , Masati Ester , Barrett Paula Q. , Gomez Ariel , Le Thu , Isakson Brant E. 
Published: June 2021

The homeostatic regulation of blood pressure by renin lineage cells in the renal vasculature and the adrenal zona glomerulosa (ZG), is crucial for controlling tissue renin expression and adrenocortical aldosterone synthesis. In the renal vasculature, renin lineage cells respond to changes in blood pressure by differentiating and re‐expressing their fetal renin gene program to compensate for lowered blood pressure. In the adrenal cortex, ZG cells of the renin lineage centripetally turnover, differentiating from an aldosterone synthetic program to a glucocorticoid synthetic one, thus maintaining steady state aldosterone production. The cellular signals coordinating these transitions is unclear, but evidence from our lab posits a role for purinergic signaling mediated by Pannexin 1 channels. We hypothesized that Pannexin 1 (Panx1) channels regulate purinergic communication and cell differentiation in the renal vasculature and adrenal cortex to regulate RAAS and blood pressure homeostasis. To test this hypothesis, we generated a novel renin cell Panx1 knockout mouse (Ren1‐Px1 KO). At baseline, mice exhibit no differences in kidney size, morphology, or plasma renin concentration. However, Ren1‐Px1 KO mice have increased plasma sodium concentration, reduced urine volume, and a significant elevation in aldosterone levels, which corresponded with aberrant expression of aldosterone synthetic enzyme (CYP11B2) and ZG cell differentiation in the adrenal cortex. Using radiotelemetry, we measured blood pressure in Ren1‐Px1 KO mice, which were hypertensive at baseline. Lastly, we assessed renin dynamics in the kidney when blood pressure is lowered. Ren1‐Px1 KO mice retain the capacity to secrete renin at baseline, but fail to completely recruit tissue renin expression in the renal vasculature. We conclude that loss of Panx1 from renin lineage cells causes activation of RAAS primarily by influencing ZG trans‐differentiation, despite changes in renal renin dynamics. Thus, Panx1 channels may be a novel regulator of long term blood pressure control.Support or Funding Information1 F31 HL1376270/NHLBI NIH P01 HL120840/NHLBI NIHThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
TRPA1‐Induced Pulmonary Spinal Sympathetic Afferent Activation is Attenuated in Rats with Chronic Heart Failure
Authors: Adam Ryan J. , Xia Zhiqiu , Shanks Julia A. , Rozanski George J. , Lisco Steven J. , Zucker Irving H. , Wang Han‐Jun 
Published: June 2021

In a recent preliminary study (Association of the University Anesthesiologists 64th annual meeting, Abstract #1109, 2017), we reported that activation of pulmonary spinal afferents by topical application of bradykinin (BK) and the TRPV1 agonist capsaisin on to lung surfaces (especially on the ventral surface) evokes a previously undocumented potent sympatho‐excitatory reflex that includes increased bood pressure (BP), heart rate (HR) and renal sympathetic nerve activity (RSNA) in urethane‐α‐chloralose anesthetized, vagotomized rats. These data suggested a new pulmonary sympathetic afferent reflex (PSAR) in rats. However, it remains unclear whether pulmonary sympathetic afferents can also be activated by the transient receptor potential ankyrin 1 (TRPA1) agonist, allyl isothiocyanate (AITC). In the current study, we examined the TRPA1‐induced PSAR in both normal and chronic heart failure (CHF) states. After bilateral vagotomy, we applied filter paper (3 × 3 mm) saturated with 30 mM AITC to the ventral lung surfaces to stimulate the PSAR in urethane‐ α‐chloralose anesthetized sham‐operated and CHF (8 weeks post myocardial infarction) rats. We found that application of AITC to the lungs resulted in a biphasic BP response whereas HR and RSNA remained elevated during the AITC application in sham rats (Table 1). Compared to sham rats, AITC caused a predominantly depressor response in CHF rats. The increases in HR and RSNA in response to AITC were also attenuated in CHF rats. These data suggest that activation of the TRPA1 receptor in pulmonary spinal afferents can cause sympatho‐excitation in normal rats whereas this response was blunted in CHF rats. Ongoing studies are validating TRPA1 receptor protein expression in pulmonary sensory neurons in sham and CHF rats.Support or Funding InformationThis work was, in part, supported by grants from the National Heart, Lung, and Blood Institute (1R01HL121012‐01 and 1R01HL126796‐01).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Autonomic Responses during Atrial Fibrillation Ablation
Authors: Cui Jian , Gonzalez Mario , Blaha Cheryl , Hill Ashley , Sinoway Lawrence I. 
Published: June 2021

Left atrial radiofrequency catheter ablation (RFCA) is a therapy for atrial fibrillation. RFCA may alter sensory input from left atrium and pulmonary veins. It is speculated that RFCA may alter autonomic afferents and alter indices of sympathetic function. Although prior studies have shown that RFCA may alter autonomic function, which was assessed with heart rate variability (HRV), the effects of left atrial RFCA on sympathetic nerve activity have not been assessed. In this study, we hypothesized that RFCA would raise muscle sympathetic nerve activity (MSNA) during and after the RFCA procedure. Total of 18 patients (16 M, 2 F, 57 ± 3 years, 181 ± 2 cm, 97 ± 5 kg) were studied. In Protocol 1 (n = 10), the ECG, BP and MSNA from the peroneal nerve were recorded through the RFCA procedure in the electrophysiology laboratory. In Protocol 2 (n = 8), ECG, BP and MSNA were recorded before (within one week) and one day after the RFCA in a research laboratory. In Protocol 1, MSNA was obtained prior (n = 9), during (n = 3) and just post (within 15 min, n = 7) the RFCA procedure. Compared to prior RFCA, MSNA decreased during (28.4 ± 3.7 to 16.0 ± 2.6 bursts/min, P < 0.05) and just post (28.6 ± 3.1 to 16.5 ± 4.1 bursts/min, P < 0.05) the RFCA. Cardiac sympathetic tone (HRV) also decreased (prior, during, post LF/HF: 0.64 ± 0.15, 0.49 ± 0.11, 0.16 ± 0.04, P < 0.05, n = 10). Vagal tone (HRV indexes: RMSSD, SDSD, HF) increased during RFCA (all P < 0.05, n = 10). In Protocol 2, MSNA increased one day after RFCA (21.3 ± 3.7 to 35.7 ± 2.6 bursts/min, P < 0.05, n = 6), and blood pressure did not change. Vagal tone (HRV indexes) decreased (all P < 0.05, n = 8), while LF/HF also tended (P = 0.09, n = 8) to decrease one day after RFCA. Despite body motions and electronic noise during the RFCA procedure, we successfully obtained MSNA recordings during the RFCA procedure. The MSNA data suggest that the sympathetic activity is suppressed, and the HRV indexes suggest that the vagal tone is activated during the procedure. We speculate that the radiofrequency energy stimulates the vagal afferents, which in turn induces the observed effects during the procedure. Our data suggest the RFCA induces autonomic denervation in the heart and induces decreases in vagal and cardiac sympathetic tone one day post procedure. The rise in the sympathetic output to muscle after the procedure may represent a compensatory response to maintain blood pressure.Support or Funding InformationSupported by American Heart Association Grant 15GRNT24480051 (Cui), Penn State Heart and Vascular Institute Penny A. Garban Endowment (Cui), National Institutes of Health Grants P01 HL096570 (Sinoway) and UL1 TR000127 (Sinoway).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Treatment with Streptozotocin (STZ) increases expression of macrophage migration inhibitory factor (MIF) but not metalloproteinase‐13 (MMP‐13) mRNA in the liver of channel catfish
Authors: Nevarez Ericka , Spainhour Rebekah , Kobayashi Yass 
Published: June 2021

Tissue repair during liver damage depends on the recruitment and activation of macrophages. In rodents, the production of MIF is essential for the recruitment of scar‐forming macrophages. In addition, production of MMP‐13 appears to be critical for successful remodeling and hepatic tissue repair. In our previous studies with channel catfish, STZ treatment induced hypoglycemia and an abnormal gross morphology of the liver and gall bladder. This suggests that the liver is the target organ for STZ in channel catfish and causes acute liver damage. This results in hypoglycemia, necrosis and eventually organ failure. However, whether liver damage induced by the STZ treatment results in recruitment and activation of macrophage in the liver of channel catfish has never been examined. Liver samples were collected from juvenile channel catfish 7 days after intraperitoneal administration of 0, 3.6, 36, 180, or 360 mg/kg STZ on day 0 (n=4 fish/treatment). Expression of genes (MMP‐13 and MIF) were measured using quantitative real‐time PCR. Expression of MIF and MMP‐13 changed in response to increases in STZ dosage (p<0.01, and p=0.05, respectively.) Expression of MMP‐13 mRNA decreased in response to an increase in STZ dosage. Expression of MIF mRNA was significantly higher in fish treated with 360 mg/kg body weight compared to control (p<0.05). Decreased expression of MMP‐13 suggests STZ treatment inhibits macrophage‐mediated tissue repair. Given that MIF has been associated with multiple liver diseases, STZ treatment may activate multiple mechanisms other than those associated with fibrosis to induce liver damage in channel catfish.Support or Funding InformationThis study is supported by Kansas Idea Network of Biomedical Research Excellence (P20GM103418).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effect of Oleanolic Acid on Inflammatory Cytokines on Rats Fed with High Fructose Diet & Metformin.
Authors: Matumba Mashudu Given , Nyakunda Trevor , Mukwevho Emmanuel 
Published: June 2021

Inflammatory cytokines are signaling molecules that play a crucial role in regulation of human immune response. Current research has demonstrated that inflammatory processes also play a significant role in the etiology of type‐2 diabetes (T2D) and obesity. High levels of circulating inflammatory concentration of cytokines have been linked to insulin resistance, the hallmark of T2D. In this study we have assessed the effect of oleanolic acid on some inflammatory cytokine biomarkers (TNF‐α, IL‐6, IL‐10, MCP‐1 and VEGF). Oleanolic acid is a plant derived compound that has shown some promising therapeutic effects on insulin resistance and T2D.In this study, Sprague Dawley rats were fed with high fructose diet (HFD) and also metformin. Analysis of inflammatory cytokines concentration in blood plasma was done using Bio‐Plex Pro magnetic bead‐based assay. Results showed that all five cytokines were decreased when OA was used and also increased when HFD was used. Similar pattern when gene expression was studied was also observed.These results clearly indicate that OA influences their concentration and also their gene expression. On the contrary HFD, showed the opposite by increasing both the concentration as well as the gene expression of these cytokines.In conclusion these study further suggests that OA plays a key role on inflammatory cytokine regulation and it can be used as an effective therapeutic agent to ameliorate insulin resistance and T2D.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Coupling of mDia1‐dependent fast endocytosis to exocytosis in pancreatic beta cells helps to maintain normal glucose tolerance in mice
Authors: Wei Lisi , Du Wen , Zhao Shiqun , Chen Liangyi 
Published: June 2021

Previously we have identified a novel Ca2+‐triggered clathrin‐independent but actin‐dependent fast endocytosis (CIE) in pancreatic beta cells. In contrast to well‐defined clathrin‐dependent endocytosis, neither the molecular mechanism nor physiological function of this clathrin‐independent endocytosis is clear. By combining patch clamp capacitance recording, super‐resolution imaging and specific molecular interventions, we have identified that an actin polymerization factor, mDia1, mediates this fast CIE in pancreatic beta‐cells. Using shRNA of mDia1 and knockout mice model, we have shown that removal of CIE leads to impaired exocytosis evoked by sustained stimulation, and disturbed glucose tolerance in mice, which cause ER stress and cellular function degeneration. Interestingly, during the progression of type II diabetes in KKAy mice, we have found out that down‐regulation of mDia1 expression and defects in fast CIE precede the dysregulation of insulin secretion in beta cells, highlighting defects of CIE may cause the beta cell failure. Overall, we conclude that exocytosis‐coupled fast CIE in pancreatic beta cells is essential to sustain insulin secretion during glucose elevation in chronic experiments, and is important for the maintaining of beta cell function and glucose tolerance in a long run.Support or Funding InformationThis study was supported by grants from the National Science and Technology Major 224 Project Program (2016YFA0500400), the Major State Basic Research Program of China 225 (2013CB531200), and the National Natural Science Foundation of China (31327901, 226 31521062, 31570839, 31428004, 61375018, and 61672253).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Determining the Mechanism by which PRDM16 Maintains the Adult Small Intestinal Epithelium
Authors: Stine Rachel , Seale Patrick 
Published: June 2021

The intestinal epithelium is a well‐organized tissue that undergoes continuous cell turnover, with most cells being replaced every 4–5 days. PRDM16 is a large zinc‐finger containing transcription factor that, in addition to its well‐studied role in brown/beige adipose, regulates maintenance of neuronal and hematopoietic stem cells. However, the role of PRDM16 in other tissues is not well understood. We find that acute global deletion of Prdm16 in adult mice causes death within ten days. The Prdm16‐deleted mice begin to lose weight and appear weak and lethargic, with visibly distended and pale intestines. Histological analysis shows that PRDM16 is selectively and highly expressed in the intestinal epithelium of the duodenum and jejunum. Apoptotic cells are prevalent in the crypt, particularly in the transit amplifying zone by 3 days after Prdm16 deletion. By 5 days after deletion, intestinal tissue appears disorganized, with an abnormal accumulation of secretory cells in the crypt that express markers of both the goblet and Paneth cell lineages, indicating defects in differentiation. Interestingly, we could detect no obvious defects in Notch signaling. We performed RNA‐seq on isolated crypts to identify candidate signaling pathways that change in the intestine shortly after global knockout of Prdm16. A striking upregulation of P53‐activated apoptotic genes occurs immediately following the disappearance of PRDM16 protein, as well as an induction of Type‐I Interferon signaling. Independent of this, we see marked downregulation of genes involved in metabolic pathways. Studying the effects of PRDM16 ex vivo, we find that enteroid culture recapitulates the phenotypes observed in vivo, with Prdm16 deletion causing induction of apoptosis and a failure of intestinal enteroids to form buds. Further, we show that shRNA mediated knockdown of Prdm16 is sufficient to block the formation of enteroids. Our phenotype is ameliorated but not fully rescued by additional deletion of p53 both in vivo and ex vivo. We are currently focusing on defects in mitochondrial function, which appear to be a second major driver of our intestinal phenotype.Support or Funding InformationNRSA NIDDK F32 DK105743‐03 Pilot Grant NIDDK P30‐DK050306This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.