| 4441. |
- Rung, Emilia, 1974, et al.
(författare)
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Depletion of substrates for protein prenylation increases apoptosis in human periovulatory granulosa cells
- 2006
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Ingår i: Molecular reproduction and development. - : Wiley. - 1040-452X .- 1098-2795. ; 73:10, s. 1277-83
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Tidskriftsartikel (refereegranskat)abstract
- Progesterone receptor (PR) stimulation promotes survival in human and rat periovulatory granulosa cells. PR antagonists, Org 31710 and RU 486, both increase apoptosis and decrease cholesterol synthesis in these cells. The decrease in cholesterol synthesis also causes decreased synthesis of other products branching from the cholesterol synthesis pathway, including substrates for protein prenylation. In this study we focus on the link between apoptosis and prenylation in human periovulatory granulosa cells. A decreased cholesterol synthesis and increased apoptosis was verified in experiments with human periovulatory granulosa cells treated with the PR antagonists Org 31710 or RU 486 by measuring caspase-3/7 activity and incorporation of 14C-acetate into cholesterol and progesterone. Correspondingly, specific inhibition of cholesterol synthesis in periovulatory human granulosa cells using HMG-CoA reductase inhibitors (lovastatin or simvastatin) increased apoptosis, measured as caspase-3/7 activity. The increase in apoptosis caused by simvastatin or Org 31710 was partially reversed by addition of the protein prenylation precursors farnesol or geranylgeraniol. In addition, the prenylation inhibitors FTI R115777 and GGTI 2147 increased apoptosis in these cells. In conclusion our data suggest that PR antagonists increase apoptosis and reduce cholesterol synthesis in periovulatory granulosa cells and that the resulting depletion of substrates for protein prenylation may contribute to the increased apoptosis sensitivity.
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| 4442. |
- Rung, Emilia, 1974, et al.
(författare)
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Progesterone-receptor antagonists and statins decrease de novo cholesterol synthesis and increase apoptosis in rat and human periovulatory granulosa cells in vitro
- 2005
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Ingår i: Biology of reproduction. - : Oxford University Press (OUP). - 0006-3363 .- 1529-7268. ; 72:3, s. 538-45
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Tidskriftsartikel (refereegranskat)abstract
- Progesterone-receptor (PR) stimulation promotes survival in rat and human periovulatory granulosa cells. To investigate the mechanisms involved, periovulatory rat granulosa cells were incubated in vitro with or without the PR-antagonist Org 31710. Org 31710 caused the expected increase in apoptosis, and expression profiling using cDNA microarray analysis revealed regulation of several groups of genes with functional and/or metabolic connections. This regulation included decreased expression of genes involved in follicular rupture, increased stress responses, decreased angiogenesis, and decreased cholesterol synthesis. A decreased cholesterol synthesis was verified in experiments with both rat and human periovulatory granulosa cells treated with the PR-antagonists Org 31710 or RU 486 by measuring incorporation of [14C]acetate into cholesterol, cholesterol ester, and progesterone. Correspondingly, specific inhibition of cholesterol synthesis in periovulatory rat granulosa cells using 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (lovastatin, mevastatin, or simvastatin) increased apoptosis, measured as DNA fragmentation and caspase-3/7 activity. The increase in apoptosis caused by simvastatin was reversed by addition of the cholesterol synthesis-intermediary mevalonic acid. These results show that PR antagonists reduce cholesterol synthesis in periovulatory granulosa cells and that cholesterol synthesis is important for granulosa cell survival.
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| 4443. |
- Rydell-Törmänen, Kristina, et al.
(författare)
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Aberrant nonfibrotic parenchyma in idiopathic pulmonary fibrosis is correlated with decreased β-catenin inhibition and increased Wnt5a/b interaction
- 2016
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Ingår i: Physiological Reports. - : Wiley. - 2051-817X. ; 4:5
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Tidskriftsartikel (refereegranskat)abstract
- Idiopathic pulmonary fibrosis (IPF), an insidious disease with grave prognosis, is characterized by heterogeneous fibrosis with densely fibrotic areas surrounded by nonfibrotic normal-looking tissue, believed to reflect a temporal development. The etiology is incompletely elucidated, but aberrant wound healing is believed to be involved. Embryonic signaling pathways, including Wnt signaling, are reactivated in wound healing, and we therefore aimed to investigate Wnt signaling, and hypothesized that Wnt signaling would correspond to degree of fibrosis. Material from 10 patients with IPF were included (four diagnostic biopsies and six donated lungs) and compared to healthy controls (n = 7). We investigated markers of Wnt signaling (β-catenin, Wnt3a, ICAT, Wnt5a/b, DAAM1 and NLK) histologically in lung parenchyma with variable degree of fibrosis. Our results suggest that Wnt signaling is significantly altered (P < 0.05) already in normal-looking parenchyma. The expression of Wnt3a and ICAT decreased (both P < 0.01) in IPF compared to healthy lungs, whereas β-catenin, Wnt5a/b, DAAM1 and NLK increased (P < 0.05 for all). ICAT is further decreased in dense fibrosis compared to normal-looking parenchyma in IPF (P < 0.001). On the basis of our results, we conclude that from a Wnt perspective, there is no normal parenchyma in IPF, and Wnt signaling corresponds to degree of fibrosis. In addition, β-catenin and Wnt5a appears coupled, and decreased inhibition of β-catenin may be involved. We suggest that the interaction between β-catenin, ICAT, and Wnt5a/b may represent an important research area and potential target for therapeutic intervention.
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| 4444. |
- Rydén Ahlgren, Åsa, et al.
(författare)
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Effects of adrenaline on longitudinal arterial wall movements and resulting intramural shear strain: a first report.
- 2009
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Ingår i: Clinical Physiology and Functional Imaging. - 1475-0961. ; 29, s. 353-359
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Tidskriftsartikel (refereegranskat)abstract
- Using ultrasound we recently demonstrated that in central elastic arteries as well as in large muscular arteries in humans there is a distinct longitudinal displacement of the arterial wall during the cardiac cycle. Further, for the first time, we also demonstrated that the inner parts of the vessel wall, the intima-media complex, in these vessels exhibit a larger longitudinal displacement than the outer part of the vessel wall, the adventitial region, introducing the presence of substantial shear strain, and thus shear stress within the vessel wall. The role of these unexplored phenomena is unknown. Here, in a first study on the longitudinal movements of the porcine common carotid artery, we show that administration of adrenaline (epinephrine) might have pronounced effects on the longitudinal displacement of the intima-media complex. In this experiment the longitudinal displacement of the intima-media complex increased >200% at the highest blood pressure levels as compared to baseline. Further, shear strain within the wall increased >250%; the longitudinal displacement of the adventitial region being smaller than that of the intima-media complex. Thus, our results indicate that adrenaline can markedly influence the longitudinal displacement of the arterial wall and the resulting shear strain, and thus shear stress, within the arterial wall. This opens up a new field within cardiovascular research, revealing a previously unknown mechanism in the circulatory system. Further studies on larger materials are needed to confirm our findings and to elucidate the underlying mechanisms and the physiological, pathophysiological and clinical implications of this phenomenon.
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| 4445. |
- Rydén Ahlgren, Åsa, et al.
(författare)
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Longitudinal displacement and intramural shear strain of the porcine carotid artery undergo profound changes in response to catecholamines
- 2012
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Ingår i: American Journal of Physiology: Heart and Circulatory Physiology. - : American Physiological Society. - 1522-1539 .- 0363-6135. ; 302:5, s. 1102-1115
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Tidskriftsartikel (refereegranskat)abstract
- Ahlgren AR, Cinthio M, Steen S, Nilsson T, Sjoberg T, Persson HW, Lindstrom K. Longitudinal displacement and intramural shear strain of the porcine carotid artery undergo profound changes in response to catecholamines. Am J Physiol Heart Circ Physiol 302: H1102-H1115, 2012. First published December 23, 2011; doi:10.1152/ajpheart.00470.2011.-The effects of catecholamines on longitudinal displacements and intramural shear strain of the arterial wall are unexplored. Therefore, the common carotid artery of five anaesthetized pigs was investigated using an in-house developed noninvasive ultrasonic technique. The study protocol included intravenous infusion of low-dose epinephrine (beta-adrenoceptor activation), as well as intravenous boluses of norepinephrine (alpha-adrenoceptor activation). Further, the effects of beta-blockade (metoprolol) were studied. There were significant positive correlations between pulse pressure and longitudinal displacement of the intima-media complex (r = 0.72; P < 0.001), as well as between pulse pressure and intramural shear strain (r = 0.48; P < 0.001). Following administration of norepinephrine, the longitudinal displacement of the intima-media complex and intramural shear strain profoundly increased (median 190%, range 102-296%, and median 141%, range 101-182%, respectively, compared with baseline), also when given during beta-blockade (median 228%, range 133-266%, and median 158%, range 152-235%, respectively). During infusion of low-dose epinephrine, the longitudinal displacement of the intima-media complex and intramural shear strain decreased (median 88%, range 69-122%, and median 69%, range 47-117%, respectively, compared with baseline). In conclusion, the present study shows, for the first time, that the longitudinal displacement and intramural shear strain of the porcine carotid artery undergo profound changes in response to catecholamines. Increase in longitudinal displacements seems to be strongly related to alpha-adrenoceptor activation. Thus metoprolol is insufficient to counteract a profound increase in longitudinal displacement and intramural shear strain following a surge of norepinephrine.
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| 4446. |
- Rådegran, Göran
(författare)
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Exercise limb blood flow response to acute and chronic hypoxia in Danish lowlanders and Aymara natives
- 2008
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Ingår i: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; 192:4, s. 531-539
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Tidskriftsartikel (refereegranskat)abstract
- Aim: The femoral artery blood flow response to submaximal, one-legged, dynamic, knee-extensor exercise was determined in acute and chronic hypoxia to investigate the hypotheses that with adaptation to chronic hypoxia blood haemoglobin increases, allowing preservation of blood flow as in normoxia. Methods: Sixteen Danish lowlanders participated, in groups of six to eight, in the experiments at sea level normoxia (FiO(2) congruent to 0.21) and acute hypoxia (FiO(2) congruent to 0.11), and chronic hypoxia after similar to 7 and 9-10 weeks at similar to 5260 m altitude breathing ambient air (FiO(2) congruent to 0.21) or a hyperoxic gas (FiO(2) congruent to 0.55). The response was compared with that in six Aymara natives. Results: The haemoglobin and haematocrit increased (P < 0.003) in the lowlanders at altitude vs. at sea level by similar to 39 and 27% respectively; i.e. to a similar (P = ns) level as in the natives. At rest, blood flow was the same (P = ns) in the lowlanders at sea level and altitude, as in the natives at altitude. During the onset of and incremental exercise, blood flow was the same (P = ns) in the lowlanders at sea level and altitude, as in the natives at altitude. Acute hypoxia increased (P < 0.05) blood flow by similar to 55% during exercise in the lowlanders at sea level. Acute hyperoxia decreased (P < 0.05) blood flow by similar to 22-29% during exercise in the lowlanders and natives at altitude. Conclusion: In chronic hypoxia, blood haemoglobin increases, allowing normalization of the elevated exercise blood flow response in acute hypoxia, and preservation of the kinetics and steady-state exercise blood flow as in normoxia, being similar as in the natives at altitude.
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| 4447. |
- Råmunddal, Truls, 1973, et al.
(författare)
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Overexpression of apolipoprotein-B improves cardiac function and increases survival in mice with myocardial infarction.
- 2009
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Ingår i: Biochemical and biophysical research communications. - : Elsevier BV. - 1090-2104 .- 0006-291X. ; 385:3, s. 336-40
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The heart produces apolipoprotein-B containing lipoproteins (apoB) whose function is not well understood. The aim of this study was to evaluate importance of myocardial apoB for cardiac function, structure and survival in myocardial infarction (MI) and heart failure (HF). METHODS AND RESULTS: MI was induced in mice (n=137) and myocardial apoB content was measured at 30 min, 3, 6, 24, 48, 120 h and 8 weeks post-MI. Transgenic mice overexpressing apoB (n=27) and genetically matched controls (n=27) were used to study the effects of myocardial apoB on cardiac function, remodeling, arrhythmias and survival after MI. Echocardiography was performed at rest and stress conditions at baseline, 2, 4 and 6 week post-MI and cumulative survival rate was registered. The myocardial apoB content increased both in the injured and the remote myocardium (p<0.05) in response to ischemic injury. ApoB mice had 2-fold higher survival rate (p<0.05) and better systolic function (p<0.05) post-MI. CONCLUSION: Overexpression of apoB in the heart increases survival and improves cardiac function after acute MI. Myocardial apoB may be an important cardioprotective system in settings such as myocardial ischemia and HF.
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| 4448. |
- Röijezon, Ulrik, et al.
(författare)
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Ländryggen
- 2019. - 1
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Ingår i: Motorisk kontroll och inlärning. - : Studentlitteratur AB. - 9789144074177 ; , s. 215-228
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Bokkapitel (refereegranskat)
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| 4449. |
- Rönn, Tina, et al.
(författare)
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Extensive changes in the transcriptional profile of human adipose tissue including genes involved in oxidative phosphorylation after a six months exercise intervention.
- 2014
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Ingår i: Acta Physiologica. - : Wiley. - 1748-1716 .- 1748-1708. ; 211:1, s. 188-200
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Tidskriftsartikel (refereegranskat)abstract
- Adipose tissue has an important function in total energy homeostasis and its dysregulation may contribute to life-style related diseases such as type 2 diabetes, cancer and cardiovascular diseases. The aim of this study was to investigate genome-wide mRNA expression in adipose tissue in healthy men before and after an exercise intervention to identify genes or pathways that mediate the beneficial effect of regular exercise. We also investigated the difference in adipose tissue mRNA expression between individuals with or without a family history of type 2 diabetes.
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| 4450. |
- Sababi, M, et al.
(författare)
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Mucus and alkali secretion in the rat duodenum : effects of indomethacin, N omega-nitro-L-arginine, and luminal acid.
- 1995
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Ingår i: Gastroenterology. - 0016-5085 .- 1528-0012. ; 109:5, s. 1526-34
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: Duodenal mucus and bicarbonate secretion appear to play an essential role in the protection of the duodenum. The aim of this study was to examine duodenal bicarbonate and mucus secretion and the effects of cyclooxygenase inhibition, nitric oxide synthase inhibition, and luminal acid.METHODS: Duodenal mucus gel thickness was measured using microelectrodes during intravital microscopy in anesthetized rats. Bicarbonate secretion was measured using back-titration.RESULTS: A continuous layer of mucus with a mean thickness of 284 +/- 11 microns (n = 35) and a mean alkaline secretion of 0.18 +/- 0.01 mumol.cm-2.min-1 were found in untreated animals. Indomethacin decreased both mucus and bicarbonate secretion by about 35%. NO synthase inhibition with N omega-nitro-L-arginine reduced mucus secretion by about 21% but increased bicarbonate secretion by 39%. Exposure of the mucosal surface to 10 mmol/L HCI increased mucus secretion by 44% and bicarbonate secretion by 22%.CONCLUSIONS: The duodenal mucus layer is continuous. It can be easily removed, and new secretion can be followed. Duodenal mucus secretion is strongly stimulated by luminal acid and endogenous prostanoids and less markedly by NO, whereas bicarbonate secretion is stimulated by acid and endogenous prostanoids and inhibited by endogenous NO.
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