| 1. |
- Andersson, Tony P. M., 1973-
(författare)
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Melanophore signaling : regulation and application
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Melanophores are pigment-containing cells responsible for quick physiological color changes in lower vertebrates due to redistribution of melanosomes, pigment granules. We have studied melanophores from African clawed frog, Xenopus laevis. Classically, melanosomes can be stimulated to aggregate in the cell center by the hormone melatonin via a process involving activation of the inhibitory Gi/o protein and inhibition of adenylate cyclase/cAMP/protein kinase A pathway. In addition, tyrosine phosphorylations have been shown to be crucial for aggregation. In this thesis, we demonstrate that mitogen-activated protein kinase (MAPK) are activated and phosphoinositol 3-kinase (PI3-K) are involved in melatonininduced aggregation. Inhibition of MAPK kinase or PI3-K inhibits MAPK activation, tyrosine phosphorylation of a 280-kDa protein and aggregation. Further, PI3-K inhibition is less dramatic in fish Labrus melanophores. Together with findings that phosphodiesterase (PDE) 4 and/or PDE2 are involved in keeping the aggregated state in Xenopus, we suggest that active PI3-K via MAPK stimulates PDE, thus lowering cAMP. We also use latrunculin A to induce aggregation via disruption of actin filaments. Kinetic studies indicate that melatonin and latrunculin share final downstream target, possibly inactivate myosin-V leading to melanosome aggregation. As biosensor application, a new computer screen assisted technique suitable for bioassays is demonstrated using melanophores to monitor kinetic responses of melanosome movement and blood plasma sample detection of the asthma drug and ß2 adrenergic agonist formoterol. We also used melanophores to examine the efficacy of enantiomers of formoterol. We confirm that (R;R)-formoterol is more potent than (S;S)-formoterol, in guinea pig tracheal ring preparations, cultured melanophores, and radioligand binding on COS-7 cells, but demonstrate and calculate that (S;S)-formoterol has more efficacy than previously described. Characterization of melanophores are important for biosensor applications, i e to understand mechanisms of drugs, and will probably also increase the knowledge of cell signaling in other cell systems.
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| 2. |
- Andersson, Tony, 1973-, et al.
(författare)
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Phosphoinositide 3-kinase is involved in Xenopus and Labrus melanophore aggregation
- 2003
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Ingår i: Cellular Signalling. - 0898-6568 .- 1873-3913. ; 15:12, s. 1119-1127
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Tidskriftsartikel (refereegranskat)abstract
- Melanophores are pigmented cells capable of quick colour changes through coordinated transport of their intracellular pigment granules. We demonstrate the involvement of phosphoinositide 3-kinase (PI3-K) in Xenopus and Labrus aggregation by the use of the PI3-K inhibitor, LY-294002. In Xenopus, wortmannin-insensitive PI3-K was found to be essential for the aggregation, mitogen-activated protein kinase (MAPK) activation and tyrosine phosphorylation of a 280-kDa protein, and for the maintenance of low cyclic adenosine 3':5'-monophosphate (cAMP) during the aggregated state. Pre-aggregated cells disperse completely to LY-294002 at 50-100 muM, involving a transient elevation in cAMP due to adenylate cyclase (AC) stimulation or to inhibition of cyclic nucleotide phosphodiesterase (PDE). The inactive analogue LY-303511 did not induce dispersion at the same concentrations. PDE4 and/or PDE2 was found to be involved in melanosome aggregation. The similar kinetics of LY-294002 and various PDE inhibitors indicates that the elevation of cAMP might be due to inhibition of PDE. In Labrus melanophores, LY-294002 had a less dramatic effect, probably due to less dependence on PDE in regulation of cAMP levels. In Xenopus aggregation, we suggest that melatonin stimulation of the Mel1c receptor via G(betagamma) activates PI3-K that, directly or indirectly via MAPK, activates PDE. (C) 2003 Elsevier Inc. All rights reserved.
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| 3. |
- Andersson, Tony, 1973-, et al.
(författare)
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Regulation of melanosome movement by MAP kinase
- 2003
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Ingår i: Pigment Cell Research. - : Wiley. - 0893-5785 .- 1600-0749. ; 16:3, s. 215-221
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Tidskriftsartikel (refereegranskat)abstract
- Our objectives were to further characterize the signaling pathways in melatonin-induced aggregation in Xenopus melanophores, specifically to investigate a possible role of mitogen-activated protein kinase (MAPK). By Western blotting we found that melatonin activates MAPK, which precedes melanosome aggregation measured in a microplate reader. Activation of MAPK, tyrosine phosphorylation of a previously described 280-kDa protein, and melanosome aggregation are sensitive to PD98059, a selective inhibitor of MAPK kinase. The MAPK activation is also decreased by the adenylate cyclase stimulant forskolin. In summary, we found that MAPK is activated during melatonin-induced melanosome aggregation. Activation was decreased by an inhibitor of MAPK kinase, and by forskolin. In addition to inhibition of cyclic adenosine 3′,5′-monophosphate (cAMP), reduction in protein kinase A activity (PKA), and activation of protein phosphatase 2A, we suggest that melatonin receptors activate the MAPK cascade and tyrosine phosphorylation of the 280-kDa protein. Although the cAMP/PKA signaling pathway is the most prominent, our data suggest that simultaneous activation of the MAPK cascade is of importance to obtain a completely aggregated state. This new regulatory mechanism of organelle transport by the MAPK cascade might be important in other eukaryotic cells.
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| 4. |
- Calles, Olle, 1974-, et al.
(författare)
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Ål i Ätran : En fallstudie för svensk ålförvaltning
- 2012
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Det europeiska ålbeståndet har minskat drastiskt under de senaste årtiondena och år 2007 antog därför EU en förordning, som innehåller åtgärder för återhämtning av beståndet av europeisk ål och som innebar att alla medlemsländer måste upprätta en nationell ålförvaltningsplan. I Sveriges ålförvaltningsplan anges minskad dödlighet i vattenkraftverk som en viktig åtgärd för att öka mängden blankålar som når havet. För att sådana åtgärder ska få stor effekt, måste man veta var mest ål produceras och vilken skada som orsakas av de kraftverk ålen passerar på sin väg mot havet. Denna kunskap är bristfällig för de flesta vattendrag i Sverige.Ätran har en lång historia som ett ålproducerande vattendrag soch lämpar sig väl för en fallstudie för svensk ålförvaltning för att belysa ålproduktionens omfattning, dess lokalisering och därmed åtgärdsnyttan. Blankålsfångst på sex platser i Ätrans avrinningsområde under 2010-2011 visade att Ätran prducerar minst 950 blankålar/år och den totala produktionen för hela Åtrans avrinningsområde skulle kunna vara >5500 blankålar/år. Vår studie visar att man utöver redan genomförda och beslutade åtgärder endast behöver åtgärda ytterligare ett kraftverk för att merparten av Åtyrans blankålar ska nå havet.
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| 5. |
- Filippini, Daniel, et al.
(författare)
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Microplate based biosensing with a computer screen aided technique
- 2003
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Ingår i: Biosensors & bioelectronics. - 0956-5663 .- 1873-4235. ; 19:1, s. 35-41
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Tidskriftsartikel (refereegranskat)abstract
- Melanophores, dark pigment cells from the frog Xenopus laevis, have the ability to change light absorbance upon stimulation by different biological agents. Hormone exposure (e.g. melatonin or α-melanocyte stimulating hormone) has been used here as a reversible stimulus to test a new compact microplate reading platform. As an application, the detection of the asthma drug formoterol in blood plasma samples is demonstrated. The present system utilizes a computer screen as a (programmable) large area light source, and a standard web camera as recording media enabling even kinetic microplate reading with a versatile and broadly available platform, which suffices to evaluate numerous bioassays. Especially in the context of point of care testing or self testing applications these possibilities become advantageous compared with highly dedicated comparatively expensive commercial systems.
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| 6. |
- Geijer, Håkan, et al.
(författare)
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Radiation dose optimization in coronary angiography and percutaneous coronary intervention (PCI) : II. Clinical evaluation
- 2002
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Ingår i: European Radiology. - : Springer Science and Business Media LLC. - 0938-7994 .- 1432-1084. ; 12:11, s. 2813-2819
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Tidskriftsartikel (refereegranskat)abstract
- In a previous part of this study, the fluoroscopy dose rate was reduced in a cardiac catheterization laboratory. The objectives of the present study were to evaluate the effects in a clinical population undergoing percutaneous coronary intervention (PCI) of the dose-reducing measures detailed previously. Kerma area-product (KAP) values were first recorded for 154 patients undergoing PCI. Then, the fluoroscopy KAP rate was reduced from 44 to 16 mGy cm2/s by increasing filtration and reducing the image intensifier dose request. After this optimization, KAP was recorded for another 138 PCI procedures. After adjustment for differing proportions of combined procedures (coronary angiography+PCI), the total KAP was reduced to 67% of the original value with a 95% confidence interval from 57 to 78%, statistically significant. The mean total KAP values were 93.6 Gy cm2 before and 69.1 Gy cm2 after optimization. The KAP for digital acquisition did not change significantly. It is possible to make a large dose reduction in PCI by reducing the fluoroscopy dose rate. This dose reduction is beneficial for both patients and staff.
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