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Phosphoinositide 3-kinase is involved in Xenopus and Labrus melanophore aggregation
Linköpings universitet, Institutionen för medicin och vård, Farmakologi. Linköpings universitet, Hälsouniversitetet.
Kristineberg Marine Research Station,Fiskebäckskil, Sweden.
Linköpings universitet, Institutionen för medicin och vård, Farmakologi. Linköpings universitet, Hälsouniversitetet.
2003 (Engelska)Ingår i: Cellular Signalling, ISSN 0898-6568, E-ISSN 1873-3913, Vol. 15, nr 12, s. 1119-1127Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

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 μM, 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 Gβγ activates PI3-K that, directly or indirectly via MAPK, activates PDE.

Ort, förlag, år, upplaga, sidor
2003. Vol. 15, nr 12, s. 1119-1127
Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
URN: urn:nbn:se:liu:diva-26779DOI: 10.1016/S0898-6568(03)00111-6Lokalt ID: 11384OAI: oai:DiVA.org:liu-26779DiVA, id: diva2:247329
Tillgänglig från: 2009-10-08 Skapad: 2009-10-08 Senast uppdaterad: 2017-12-13Bibliografiskt granskad
Ingår i avhandling
1. Melanophore signaling: regulation and application
Öppna denna publikation i ny flik eller fönster >>Melanophore signaling: regulation and application
2003 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

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.

Ort, förlag, år, upplaga, sidor
Linköping: Linköpings universitet, 2003. s. 64
Serie
Linköping University Medical Dissertations, ISSN 0345-0082 ; 799
Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
urn:nbn:se:liu:diva-27457 (URN)12110 (Lokalt ID)91-7373-485-3 (ISBN)12110 (Arkivnummer)12110 (OAI)
Disputation
2003-09-05, Aulan, Administrationshuset, Hälsouniversitet, Linköping, 13:00 (Svenska)
Opponent
Tillgänglig från: 2009-10-08 Skapad: 2009-10-08 Senast uppdaterad: 2012-10-12Bibliografiskt granskad

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Andersson, TonySvensson, Samuel

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