Current research in physiology最新文献

{"title":"Adrenergic control of the cardiovascular system in deer mice native to high altitude","authors":"Oliver H. Wearing ,&nbsp;Derek Nelson ,&nbsp;Catherine M. Ivy ,&nbsp;Dane A. Crossley II ,&nbsp;Graham R. Scott","doi":"10.1016/j.crphys.2022.01.006","DOIUrl":"10.1016/j.crphys.2022.01.006","url":null,"abstract":"<div><p>Studies of animals native to high altitude can provide valuable insight into physiological mechanisms and evolution of performance in challenging environments. We investigated how mechanisms controlling cardiovascular function may have evolved in deer mice (<em>Peromyscus maniculatus</em>) native to high altitude. High-altitude deer mice and low-altitude white-footed mice (<em>P. leucopus</em>) were bred in captivity at sea level, and first-generation lab progeny were raised to adulthood and acclimated to normoxia or hypoxia. We then used pharmacological agents to examine the capacity for adrenergic receptor stimulation to modulate heart rate (<em>f</em>_H) and mean arterial pressure (<em>P</em>_mean) in anaesthetized mice, and used cardiac pressure-volume catheters to evaluate the contractility of the left ventricle. We found that highlanders had a consistently greater capacity to increase <em>f</em>_H via pharmacological stimulation of β₁-adrenergic receptors than lowlanders. Also, whereas hypoxia acclimation reduced the capacity for increasing <em>P</em>_mean in response to α-adrenergic stimulation in lowlanders, highlanders exhibited no plasticity in this capacity. These differences in highlanders may help augment cardiac output during locomotion or cold stress, and may preserve their capacity for α-mediated vasoconstriction to more effectively redistribute blood flow to active tissues. Highlanders did not exhibit any differences in some measures of cardiac contractility (maximum pressure derivative, d<em>P</em>/dt_max, or end-systolic elastance, E_es), but ejection fraction was highest in highlanders after hypoxia acclimation. Overall, our results suggest that evolved changes in sensitivity to adrenergic stimulation of cardiovascular function may help deer mice cope with the cold and hypoxic conditions at high altitude.</p></div>","PeriodicalId":72753,"journal":{"name":"Current research in physiology","volume":"5 ","pages":"Pages 83-92"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829085/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39927864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intergenerational protein deficiency and adolescent reproductive function of subsequent female generations (F1 and F2) in rat model","authors":"Nosarieme O. Abey,&nbsp;Osaretin A.T. Ebuehi,&nbsp;Ngozi O.A. Imaga","doi":"10.1016/j.crphys.2021.12.003","DOIUrl":"10.1016/j.crphys.2021.12.003","url":null,"abstract":"<div><h3>Background</h3><p>Efficient reproductive function is an important characteristic that has evolved through natural selection. Nutrition can modulate reproductive activities at different levels, and its effect on reproduction is deemed complex and less predictable.</p></div><div><h3>Objective</h3><p>This study aims at investigating the underlying effect of persistent dietary protein deficiency during early life on reproductive parameters of subsequent (F₁ and F₂) generations.</p></div><div><h3>Method</h3><p>Rats in group of four (4) were fed daily, different ration of protein diet (PD) formulated as: 21% protein diet, 10%protein diet, 5%protein diet and control diet (rat chow, containing 16–18% protein). They were fed <em>ad libitum</em> before mating, throughout gestation and lactation, and next generations were weaned to the maternal diet. Reproductive function analysis (which include; gestation and pubertal hormonal profiling, onset of puberty, oestrus cyclicity, sexual response) and morphometric analysis of the ovarian structure were carried out to assess associated consequences.</p></div><div><h3>Results</h3><p>There was significant reduction in the fertility index (Control; 85.8%., 21%PD; 88.43%., as compared to 10%PD; 65.9%., 5%PD; 35.78%.,) at F_1, also recurring in F₂ respectively as a consequence of altered reproductive function in the protein deficient models at P ≤ 0.05. Low protein diet posed suboptimal intrauterine condition, which was linked to increased prenatal morbidity and mortality (control; 11.3%., 21%PD; 3.3%., 10%PD; 27.4%., 5%PD; 32.9%), low birthweight (control; 5.29, 4.9 g., 21%PD; 5.5, 5.06 g., 10%PD; 4.05, 3.86 g., 5%PD; 2.7, 2.5 g) at F₁ and F₂ respectively, delayed onset of puberty (with average pubertal age set at: control; PND 36, 21%PD; PND 38 while 10%PD; PND 62., and 5%PD; PND 67), followed by induced cycle irregularity, altered follicular maturation and endocrine dysfunction, more severe in 5%PD.</p></div><div><h3>Conclusion</h3><p>Reproductive status of a female organism depends on the maintenance of ovarian structure and function that has been associated with the hypothalamic pituitary-gonadal axis, hormonal events and sexual maturity. There is therefore an association between persistent early life protein deficiency and reproductive response which mechanistically involves life-long changes in key ovarian cytoarchitecture and function.</p></div>","PeriodicalId":72753,"journal":{"name":"Current research in physiology","volume":"5 ","pages":"Pages 16-24"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e6/e7/main.PMC8724923.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39930860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term effects of multiple concussions on prefrontal cortex oxygenation during neurovascular coupling activation in retired male contact sport athletes","authors":"Luke W. Sirant ,&nbsp;Jyotpal Singh ,&nbsp;Steve Martin ,&nbsp;Catherine A. Gaul ,&nbsp;Lynneth Stuart-Hill ,&nbsp;Darren G. Candow ,&nbsp;Cameron Mang ,&nbsp;J. Patrick Neary","doi":"10.1016/j.crphys.2022.11.002","DOIUrl":"10.1016/j.crphys.2022.11.002","url":null,"abstract":"<div><h3>Purpose</h3><p>This study aimed to investigate the long-term effects of multiple concussions on prefrontal cortex oxygenation during a neurovascular coupling activating task using near infrared spectroscopy (NIRS).</p></div><div><h3>Methods</h3><p>Self-reported physically active males who previously participated in contact team sports at various levels of competition and who previously had experienced at least 3 concussions (n = 55; mTBI) or had no history of concussions (n = 29; CTRL) were recruited. Participants completed a 5 min “Where's Waldo” object identification protocol which consisted of participants closing their eyes for 20-s followed by 40-s (repeated 5 times over 5-min) of searching a computer screen for “Waldo” hidden in a field of distractors. NIRS (μM) was used to measure right and left prefrontal cortex cerebral oxygenation. Oxygenated (O₂Hb), deoxygenated (HHb), total (tHb) haemoglobin, and haemoglobin difference (HbDiff) were analysed through the change in average maximal and minimal values (ΔMAX), Z-scores, and standard deviations.</p></div><div><h3>Results</h3><p>There were no significant differences in the relative change in cerebral oxygenation of the right prefrontal cortex between groups. In mTBI, left prefrontal cortex HHb ΔMAX (p = 0.031) and tHb ΔMAX (p = 0.044) were significantly lower than in the CTRL group. Within-group, right vs. left prefrontal cortex differences showed significantly lower values in left HbDiff Z-scores (p = 0.019) in only the mTBI group while the CTRL group showed significantly lower values in left HbDiff SD (p = 0.045).</p></div><div><h3>Conclusion</h3><p>This preliminary study suggests that there are changes in prefrontal cortex oxygenation in males who had a history of experiencing multiple concussions in their past during a neurovascular coupling activating task. These changes may represent potential long-term effects in the brain's ability to adapt cerebral oxygenation during increased neural activity.</p></div>","PeriodicalId":72753,"journal":{"name":"Current research in physiology","volume":"5 ","pages":"Pages 421-428"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/3b/03/main.PMC9713254.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35254876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic dysfunctions promoted by AIN-93G standard diet compared with three obesity-inducing diets in C57BL/6J mice","authors":"Lais Marinho Aguiar ,&nbsp;Carolina Soares de Moura ,&nbsp;Cintia Reis Ballard ,&nbsp;Aline Rissetti Roquetto ,&nbsp;Juliana Kelly da Silva Maia ,&nbsp;Gustavo H.B. Duarte ,&nbsp;Larissa Bastos Eloy da Costa ,&nbsp;Adriana Souza Torsoni ,&nbsp;Jaime Amaya-Farfan ,&nbsp;Mário R. Maróstica Junior ,&nbsp;Cinthia Baú Betim Cazarin","doi":"10.1016/j.crphys.2022.11.001","DOIUrl":"10.1016/j.crphys.2022.11.001","url":null,"abstract":"<div><p>Researchers from different fields have studied the causes of obesity and associated comorbidities, proposing ways to prevent and treat this condition by using a common animal model of obesity to create a profound energy imbalance in young adult rodents. However, to confirm the harmful effects of consuming a high-fat and hypercaloric diet, it is common to include normolipidic and normocaloric control groups in the experimental protocols. This study compared the effect of three experimental diets described in the literature – namely, a high-fat diet, a high-fat and high-sucrose diet, and a high-fat and high-fructose diet – to induce obesity in C57BL/6 J mice with the standard AIN-93G diet as a control. We hypothesize that the AIN diet formulation is not a good control in this type of experiment because this diet promotes weight gain and metabolic dysfunctions similar to the hypercaloric diet. The metabolic data of animals fed the AIN-93G diet were similar to those of the high-calorie groups (development of steatosis and hyperlipidemia). However, it is important to emphasize that the group fed a high-fat diet had a higher percentage of total fat (p = 0.0002) and abdominal fat (p = 0.013) compared to the other groups. Also, the high-fat group responded poorly to glucose and insulin tolerance tests, showing a picture of insulin resistance. As expected, the intake of the AIN-93G diet promotes metabolic alterations in the animals like the high-fat formulations. Therefore, although this diet continues to be used as the gold standard for growth and maintenance, it warrants a reassessment of its composition to minimize the metabolic changes observed in this study, thus updating its fitness as a normocaloric model of a standard rodent diet.</p></div>","PeriodicalId":72753,"journal":{"name":"Current research in physiology","volume":"5 ","pages":"Pages 436-444"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/51/de/main.PMC9713253.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35254877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of collagen deposition in the trout heart during thermal acclimation","authors":"Elizabeth F. Johnston,&nbsp;Todd E. Gillis","doi":"10.1016/j.crphys.2022.02.004","DOIUrl":"10.1016/j.crphys.2022.02.004","url":null,"abstract":"<div><p>The passive mechanical properties of the vertebrate heart are controlled in part by the composition of the extracellular matrix (ECM). Changes in the ECM, caused by increased blood pressure, injury or disease can affect the capacity of the heart to fill with blood during diastole. In mammalian species, cardiac fibrosis caused by an increase in collagen in the ECM, leads to a loss of heart function and these changes in composition are considered to be permanent. Recent work has demonstrated that the cardiac ventricle of some fish species have the capacity to both increase and decrease collagen content in response to thermal acclimation. It is thought that these changes in collagen content help maintain ventricle function over seasonal changes in environmental temperatures. This current work reviews the cellular mechanisms responsible for regulating collagen deposition in the mammalian heart and proposes a cellular pathway by which a change in temperature can affect the collagen content of the fish ventricle through mechanotransduction. This work specifically focuses on the role of transforming growth factor β1, MAPK signaling pathways, and biomechanical stretch in regulating collagen content in the fish ventricle. It is hoped that this work increases the appreciation of the use of comparative models to gain insight into phenomenon with biomedical relevance.</p></div>","PeriodicalId":72753,"journal":{"name":"Current research in physiology","volume":"5 ","pages":"Pages 99-108"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2665944122000116/pdfft?md5=ef7466eacb41bd15fdee92575b079a7f&pid=1-s2.0-S2665944122000116-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45097615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reproductive effects of Abelmoschus esculentus fruit methanol extract in female Wistar rats","authors":"Eunice Ogunwole ,&nbsp;Jemimah Adoh Yakubu ,&nbsp;Vivian Tally Giwa","doi":"10.1016/j.crphys.2022.05.001","DOIUrl":"10.1016/j.crphys.2022.05.001","url":null,"abstract":"<div><p>Current researches aim at identifying modifiable risk factors for infertility, particularly dietary lifestyle. <em>Abelmoschus esculentus</em> is one of the important vegetables in the human diet with reported valuable nutrients but has been linked with reproductive dysfunction in males. This study investigated the reproductive effects of <em>Abelmoschus esculentus</em> fruit methanol extract in female Wistar rats. Dried <em>Abelmoschus esculentus</em> fruit was extracted with methanol. Fifteen female Wistar rats (180–200 g) grouped into three (n = 5) received 1.0 mL/kg/day distilled water (control), 70 and 200 mg/kg/day of the extract once daily for 21 days via oral gavage. The estrous cycle was assessed using Marcondes and Papanicolaou methods. The histology of the tissues was evaluated by microscopy. Serum follicle-stimulating hormone, luteinizing hormone, and estrogen levels were measured using an enzyme-linked immunosorbent assay. Tissue antioxidant activities and malondialdehyde levels were assayed by spectrophotometry. Data were analyzed using the Analysis of variance at a significance of p &lt; 0.05. The estrous cycle of the <em>Abelmoschus esculentus</em> fruit methanol extracts treated rats showed normal cellular characteristics. Though <em>Abelmoschus esculentus</em> fruit methanol extract increased the antioxidant activities, it reduced the body weight and follicle-stimulating hormone level and caused severe inflammation and fibrosis of the ovary and uterus. <em>Abelmoschus esculentus</em> fruit methanol extract adversely altered the reproductive functions of female Wistar rats by disrupting the ovarian and uterine cytology and reducing hormone levels.</p></div>","PeriodicalId":72753,"journal":{"name":"Current research in physiology","volume":"5 ","pages":"Pages 208-215"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2665944122000207/pdfft?md5=d125c38e01b5a23f9c14324b05c4d8d4&pid=1-s2.0-S2665944122000207-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45149478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sustained hypoxia in mice increases parasympathetic but not sympathetic tone","authors":"Juliana R. Souza,&nbsp;Mauro de Oliveira,&nbsp;Benedito H. Machado","doi":"10.1016/j.crphys.2022.09.006","DOIUrl":"10.1016/j.crphys.2022.09.006","url":null,"abstract":"<div><p>The autonomic profile of mice submitted to sustained hypoxia (SH) was not yet fully evaluated. Herein, we characterized the cardiovascular and autonomic profile of conscious freely moving mice submitted to SH using two sequential experimental protocols to evaluate the parasympathetic and sympathetic tone to the heart and the sympathetic tone to the vascular resistance. In the first protocol the sequence of antagonists was methyl-atropine followed by propranolol and then by prazosin, while in the second protocol the sequence was propranolol followed by methyl-atropine and then by prazosin. In SH the baseline heart rate was significantly lower than in control mice and the antagonism of the parasympathetic and sympathetic tone to the heart in both experimental protocols indicated an increased parasympathetic tone in SH mice and no changes in the sympathetic tone. Antagonism of the sympathetic tone to the vascular resistance with prazosin produced similar changes in arterial pressure in control and SH mice. Altogether these findings support the concept that mice submitted to SH present a significant increase in the parasympathetic but not in the sympathetic tone, which may explain why the baseline arterial pressure was not increased in SH mice.</p></div>","PeriodicalId":72753,"journal":{"name":"Current research in physiology","volume":"5 ","pages":"Pages 361-368"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/51/cd/main.PMC9516409.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40389017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Urine color expressed in CIE L*a*b* colorspace during rapid changes in hydration status","authors":"Tory Edwards,&nbsp;Michael J. Buono","doi":"10.1016/j.crphys.2022.06.007","DOIUrl":"10.1016/j.crphys.2022.06.007","url":null,"abstract":"<div><h3>Background</h3><p>To investigate how rapid changes in hydration affect urine color expressed in CIE L*a*b* colorspace.</p></div><div><h3>Methods</h3><p>This study was a two-day crossover design where subjects (N = 30) came in one visit dehydrated, after a 15 h overnight fluid deprivation, and rapidly rehydrated by drinking at least 1000 mL of water in 2 h. On the other visit subjects reported euhydrated and then rapidly dehydrated 2% by walking (3 mph) in a heat chamber (100°F, 50% humidity) for 2 h. Urine samples on both days were collected pre- and post-dehydration/rehydration. Urine osmolality, urine specific gravity, subjective urine color and objective urine color expressed in CIE L*a*b* colorspace were measured.</p></div><div><h3>Results</h3><p>In the dehydration trial participants experienced a significant weight loss of approximately 2% of their starting, euhydrated body weight. The CIE urine color L*-value significantly decreased (−2.3 units) while the b*-value significantly increased (16 units). Subjective urine color significantly increased (1 unit). Urine osmolality increased (25 mmol/kg) and urine specific gravity increased (0.002 g/mL) between the pre- and post-dehydration conditions, however, neither of these changes were statistically significant. In the rehydration trial participants had a significant 1.5% increase in body weight after the ingestion of water. Significant increases were observed in the CIE urine color L*-value (7 units) and a*-value (1.1 units), while the b*-value significantly decreased (−24 units). Subjective urine color significantly decreased (−3 units). Urine osmolality (−600 mmol/kg) and urine specific gravity (−0.018 g/mL) significantly decreased between the pre- and post-rehydration conditions.</p></div><div><h3>Conclusions</h3><p>Traditional markers of hydration, including urine osmolality and urine specific gravity, did not significantly change in the acute dehydration trial, suggesting that these values may not be responsive to rapid changes in hydration status. However, the CIE L*- and b*-values of urine color significantly decreased in the rapid dehydration trial and significantly increased in the rapid rehydration trial. Thus, the results of the current study suggest that urine color L*- and b*-values expressed in the CIE L*a*b* colorspace were more responsive to changes in hydration status during rapid dehydration than traditional indices of urine concentration and thus may be better markers under such conditions.</p></div>","PeriodicalId":72753,"journal":{"name":"Current research in physiology","volume":"5 ","pages":"Pages 251-255"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c3/fe/main.PMC9253385.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40480545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of cardiac ryanodine receptor function by the cyclic-GMP dependent protein kinase G","authors":"Luis A. Gonano ,&nbsp;Hamish M. Aitken-Buck ,&nbsp;Akash D. Chakraborty ,&nbsp;Luke P.I. Worthington ,&nbsp;Tanya R. Cully ,&nbsp;Regis R. Lamberts ,&nbsp;Martin G. Vila-Petroff ,&nbsp;Peter P. Jones","doi":"10.1016/j.crphys.2022.03.004","DOIUrl":"10.1016/j.crphys.2022.03.004","url":null,"abstract":"<div><h3>Background</h3><p>The cGMP-dependent protein kinase G (PKG) phosphorylates the cardiac ryanodine receptor (RyR2) <em>in vitro</em>. We aimed to determine whether modulation of endogenous PKG alters RyR2-mediated spontaneous Ca²⁺ release and whether this effect is linked to a change in RyR2 phosphorylation.</p></div><div><h3>Methods</h3><p>&amp; Results: Human embryonic kidney (HEK293) cells with inducible RyR2 expression were treated with the cGMP analogue 8-Br-cGMP (100 μM) to activate endogenous PKG. In cells transfected with luminal Ca²⁺ sensor, D1ER, PKG activation significantly reduced the threshold for RyR2-mediated spontaneous Ca²⁺ release (93.9 ± 0.4% of store size with vehicle vs. 91.7 ± 0.8% with 8-Br-cGMP, <em>P</em> = 0.04). Mutation of the proposed PKG phosphorylation sites, S2808 and S2030, either individually or as a combination, prevented the decrease in Ca²⁺ release threshold induced by endogenous PKG activation. Interestingly, despite a functional dependence on expression of RyR2 phosphorylation sites, 8-Br-cGMP activation of PKG did not promote a detectable change in S2808 phosphorylation (<em>P</em> = 0.9). Paradoxically, pharmacological inhibition of PKG with KT 5823 (1 μM) also reduced the threshold for spontaneous Ca²⁺ release through RyR2 without affecting S2808 phosphorylation. Silencing RNA knockdown of endogenous PKG expression also had no quantifiable effect on RyR2 S2808 phosphorylation (<em>P</em> = 0.9). However, unlike PKG inhibition with KT 5823, PKG knockdown did not alter spontaneous Ca²⁺ release propensity or luminal Ca²⁺ handling.</p></div><div><h3>Conclusion</h3><p>In an intact cell model, activation of endogenous PKG reduces the threshold for RyR2-mediated spontaneous Ca²⁺ release in a manner dependent on the RyR2 phosphorylation sites S2808 and S2030. This study clarifies the regulation of RyR2 Ca²⁺ release by endogenous PKG and functionally implicates the role of RyR2 phosphorylation.</p></div>","PeriodicalId":72753,"journal":{"name":"Current research in physiology","volume":"5 ","pages":"Pages 171-178"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2665944122000165/pdfft?md5=0834dd5168204aa7c6caafe5dbd9ce07&pid=1-s2.0-S2665944122000165-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46707191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effects of voluntary wheel running during weight-loss on biomarkers of hepatic lipid metabolism and inflammation in C57Bl/6J mice","authors":"Joshua S. Wooten,&nbsp;Kaylee E. Poole,&nbsp;Matthew P. Harris,&nbsp;Brianne L. Guilford,&nbsp;Megan L. Schaller,&nbsp;David Umbaugh,&nbsp;Andrew Seija","doi":"10.1016/j.crphys.2022.01.003","DOIUrl":"10.1016/j.crphys.2022.01.003","url":null,"abstract":"<div><p>The aim of this study was to determine the effect of voluntary wheel running (VWR) during weight-loss on hepatic lipid and inflammatory biomarkers using a murine model. To induce obesity, male C57Bl/6 mice were fed a 60% high-fat diet (HF) for 10 weeks. At 10 weeks, weight-loss was promoted by randomizing HF-fed mice to a normal diet (ND) either with (WL + VWR) or without (WL) access to running wheels for 8 weeks. Age-matched dietary control mice were fed either a ND or HF for 18 weeks. Following weight-loss, WL + VWR had a lower body mass compared to all groups despite an average weekly caloric consumption comparable to HF mice. WL + VWR had an increased adiponectin concentration when compared to WL, but no difference between WL and WL + VWR was observed for plasma glucose and lipid biomarkers. When compared to HF, the lower hepatic total lipids in both WL and WL + VWR were associated with increased pAMPK:AMPK and reduced pACC-1:ACC-1 ratios. When compared to WL, WL + VWR resulted in lower hepatic cholesterol and trended to lower hepatic triglyceride. In both WL and WL + VWR, pNF-κB p65:NF-κB p65 ratio was lower than HF and comparable to ND. TGFβ1 and BAMBI protein levels were evaluated as biomarkers for hepatic fibrosis. No differences in TGFβ1 was observed between groups; however, WL and WL + VWR had BAMBI protein levels comparable to ND. Overall, the addition of voluntary exercise resulted in greater weight-loss and improvements in hepatic cholesterol and triglyceride levels; however, limited improvements in hepatic inflammation were observed when compared to weight-loss by diet alone.</p></div>","PeriodicalId":72753,"journal":{"name":"Current research in physiology","volume":"5 ","pages":"Pages 63-72"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/fa/f7/main.PMC8814598.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39781502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}