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- Berg, Cecilia, et al.
(author)
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Platelet-induced growth of human fibroblasts is associated with an increased expression of 5-lipoxygenase.
- 2006
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In: Thrombosis and haemostasis. - 0340-6245. ; 96:5, s. 652-9
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Journal article (peer-reviewed)abstract
- Proliferation of fibroblasts is vital for adequate wound healing but is probably also involved in different hyperproliferative disorders such as atherosclerosis and cancer. The regeneration of tissue usually starts with coagulation, involving release of mitogenic and inflammatory factors from activated platelets. This study focuses on the role of eicosanoids in the proliferative effects of platelets on human fibroblasts. We show that the phospholipase A (2) inhibitor 7,7-dimethyl-5,8-eicosadienoic acid (DMDA), the combined cyclooxygenase (COX) and lipoxygenase (LOX) inhibitor 5,8,11,14-eicosatetraynoic acid (ETYA) and the LOX inhibitor 5,8,11-eicosatriynoic acid (ETI) block the platelet-induced proliferation of serum starved subconfluent human fibroblasts. Anti-proliferative effects were also obtained by specific inhibition of 5-LOX with 5,6-dehydro arachidonic acid (5,6-dAA), whereas the 12-LOX inhibitor cinnamyl-3,4-dihydroxy- a -cyanocinnamate (CDC) did not affect the platelet-stimulated growth of fibroblasts. The expression of 5-LOX was analyzed by reverse-transcriptase-mediated PCR (RT-PCR), Western blotting and HPLC. 5-LOX message and protein was detected in fibroblasts but not in platelets. Incubation with platelets markedly increased, already after one hour, the expression of 5-LOX in the fibroblast culture. The increased 5-LOX activity was associated with an elevated level of the 5-LOX metabolite 5-hydroxyeicosatetraenoic acid (5-HETE) reaching its maximum after 1 - 2 hours of co-incubation of fibroblasts and platelets. The 5-HETE production was reduced by the inhibitors DMDA, ETYA and ETI. In conclusion, this study suggests that platelet-stimulated proliferation of fibroblasts is mediated by an increased 5-LOX activity, which supports recent findings indicating a crucial role for this enzyme in proliferative disorders such as atherosclerosis.
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| 3. |
- Berg, Cecilia, 1976-, et al.
(author)
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Platelet-induced growth of human fibroblasts is associated with an increased expression of 5-lipoxygenase
- 2006
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In: Thrombosis and Haemostasis. - 0340-6245 .- 2567-689X. ; 96:5, s. 652-659
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Journal article (peer-reviewed)abstract
- Proliferation of fibroblasts is vital for adequate wound healing but is probably also involved in different hyperproliferative disorders such as atherosclerosis and cancer. The regeneration of tissue usually starts with coagulation, involving release of mitogenic and inflammatory factors from activated platelets. This study focuses on the role of eicosanoids in the proliferative effects of platelets on human fibroblasts. We show that the phospholipase A2 inhibitor 7,7-dimethyl-5,8-eicosadienoic acid (DMDA), the combined cyclooxygenase (COX) and lipoxygenase (LOX) inhibitor 5,8,11,14-eicosatetraynoic acid (ETYA) and the LOX inhibitor 5,8,11-eicosatriynoic acid (ETI) block the platelet-induced proliferation of serum starved subconfluent human fibroblasts. Anti-proliferative effects were also obtained by specific inhibition of 5-LOX with 5,6-dehydro arachidonic acid (5,6-dAA), whereas the 12-LOX inhibitor cinnamyl-3,4-dihydroxy-α-cyanocinnamate (CDC) did not affect the platelet-stimulated growth of fibroblasts. The expression of 5-LOX was analyzed by reverse-transcriptase-mediated PCR (RT-PCR), Western blotting and HPLC. 5-LOX message and protein was detected in fibroblasts but not in platelets. Incubation with platelets markedly increased, already after one hour, the expression of 5-LOX in the fibroblast culture. The increased 5-LOX activity was associated with an elevated level of the 5-LOX metabolite 5-hydroxyeicosatetraenoic acid (5-HETE) reaching its maximum after 1-2 hours of co-incubation of fibroblasts and platelets. The 5-HETE production was reduced by the inhibitors DMDA, ETYA and ETI. In conclusion, this study suggests that platelet-stimulated proliferation of fibroblasts is mediated by an increased 5-LOX activity, which supports recent findings indicating a crucial role for this enzyme in proliferative disorders such as atherosclerosis. © 2006 Schattauer GmbH, Stuttgart.
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- Dahlqvist, Per, et al.
(author)
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Environmental enrichment reverses learning impairment in the Morris water maze after focal cerebral ischemia in rats
- 2004
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In: European Journal of Neuroscience. - 0953-816X .- 1460-9568. ; 19:8, s. 2288-2298
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Journal article (peer-reviewed)abstract
- Cognitive impairment is common after ischemic stroke. In rodent stroke models using occlusion of the middle cerebral artery (MCA) this is reflected by impaired spatial memory associated with the size of the ischemic lesion. Housing in an enriched environment enhances brain plasticity and improves recovery of sensorimotor functions after experimental stroke in rats. In this study we report that postischemic housing in an enriched environment also attenuates the long-term spatial memory impairment after MCA occlusion and extinguishes the association between spatial memory and infarct volume. An enriched environment did not significantly alter the expression of selected neuronal plasticity-associated genes 1 month after MCA occlusion, indicating that most of the adaptive changes induced by an enriched environment have already occurred at this time point. We conclude that the attenuated memory impairment induced by environmental enrichment after MCA occlusion provides a useful model for further studies on the neurobiological mechanisms of recovery of cognitive functions after ischemic stroke.
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- Elcadi, Guilherme H., et al.
(author)
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A Strong Correlation Between Dorsolateral Prefrontal Cortex And Vastus Lateralis Activity During Running To Fatigue
- 2016
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In: Medicine and science in sports and exercise. - : Ovid Technologies (Wolters Kluwer Health). - 0195-9131 .- 1530-0315. ; 48:5, s. 854-854
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Journal article (peer-reviewed)abstract
- Fatigue is a phenomenon of pronounced importance in sports. Recently, there is strong evidence of interplay between the prefrontal cortex and motor output during fatiguing contractions. The dorsolateral prefrontal cortex (DLPC) due to its large involvement in cognitive and motor activities is believed to be involved but this requires physiological clarification. AIM: We investigated the relationship between DLPC activity - responses in oxyhemoglobin (HbO2) and total hemoglobin (HbT) measured by near-infrared spectroscopy (NIRS), and the vastus lateralis muscle (VL) activity - quantified as root-mean-square (RMS) of the EMG signal, during a fatigue protocol.METHODS: Four male runners (32±12 yrs) with probes for NIRS over the DLPC and EMG over the VL performed a track running test at a constant speed to fatigue (exhaustion). The running speed was individually determined as the average speed of a 1200-m time trial performed ~3 days prior to testing. For NIRS changes in μmole/L of HbO2 and HbT were computed. The VL EMG-RMS of the contraction of each step was normalized as a percent of a submaximal reference contraction (%RMS), thus removing the non-activity between steps. Data of 10s epochs at 20, 40, 60, 80 and 100% of time for each lap were averaged for analyses. Regression analyses performed with HbO2 and with HbT as dependent variables and %RMS as the independent variable.RESULTS: Over time there was an increase in HbO2 and HbT in the DLPC, and in VL-%RMS. Both HbO2 and HbT correlated strongly with EMG-RMS during running to fatigue (see figures below); p<0.001 for both.CONCLUSION: The strong relationship between DLPC and VL activities during running to fatigue suggests the involvement of the DLPC in the central processing of fatigue.
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