Sfingosiini-1-P reseptorit

 S1P kuuluu  niihin lysofasfolipideihin (LPL)  joita sfingomyeliinin kataboliasta muodostuu. Alla on mainittu myös lysofosfatidaatti LPA. Sillöäkin on omat reseptiorit.

Lysophospholipid receptor

From Wikipedia, the free encyclopedia

The lysophospholipid receptor (LPL-R) group are members of the G protein-coupled receptor family of integral membrane proteins that are important for lipid signaling.^[1] In humans, there are eight LPL receptors, each encoded by a separate gene. These LPL receptor genes are also sometimes referred to as "Edg” (an acronym for endothelial differentiation gene).

Contents

• 1 Ligands
• 2 Origin of name
• 3 Function
• 4 Group members
• 5 See also
• 6 References
• 7 External links

Ligands

The ligands for LPL-R group are the lysophospholipid extracellular signaling molecules, lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P).

Origin of name

The term lysophospholipid (LPL) refers to any phospholipid that is missing one of its two O-acyl chains. Thus, LPLs have a free alcohol in either the sn-1 or the sn-2 position. The prefix 'lyso-' comes from the fact that lysophospholipids were originally found to be hemolytic, however it is now used to refer generally to phospholipids missing an acyl chain. LPLs are usually the result of phospholipase A-type enzymatic activity on regular phospholipids such as phosphatidylcholine or phosphatidic acid, although they can also be generated by the acylation of glycerophospholipids or the phosphorylation of monoacylglycerols. Some LPLs serve important signaling functions such as lysophosphatidic acid.

Function

LPL receptor ligands bind to and activate their cognate receptors located in the cell membrane. Depending on which ligand, receptor, and cell type is involved, the activated receptor can have a range of effects on the cell. These include primary effects of inhibition of adenylyl cyclase and release of calcium from the endoplasmic reticulum, as well as secondary effects of preventing apoptosis and increasing cell proliferation.^[2]

Group members

The following is a list of the eleven known human LPL receptors:^[1][3][4]

Gene Symbol	IUPHAR Symbol	Gene / Protein Name	Agonist Ligand	Synonyms
LPAR1	272	lysophosphatidic acid receptor 1	LPA	EDG2
LPAR2	273	lysophosphatidic acid receptor 2	"	EDG4
LPAR3	274	lysophosphatidic acid receptor 3	"	EDG7
LPAR4	LPA4	lysophosphatidic acid receptor 4	"	GPR23
LPAR5	LPA5	lysophosphatidic acid receptor 5	"	GPR92
LPAR6	LPA6	lysophosphatidic acid receptor 6	"	P2RY5
S1PR1	275	sphingosine-1-phosphate receptor 1	S1P	EDG1
S1PR2	276	sphingosine-1-phosphate receptor 2	"	EDG5
S1PR3	277	sphingosine-1-phosphate receptor 3	"	EDG3
S1PR4	278	sphingosine-1-phosphate receptor 4	"	EDG6
S1PR5	279	sphingosine-1-phosphate receptor 5	"	EDG8

See also

• Lipid signaling
• Gintonin

Case: Keuhkoödema, akuutti keuhkoendoteelivaurio

 Normaalissa  lipidimembraanin  uudistumisessa osa sfingomyeliini katabolisoituu ja osa  keramidisesta molekyylistä  voi uudelleen palautua  sfingomyeliiniksi kin muta aina pieni osa muodosta S1P- sfingosiini-1 fosfaattia jolla on niitä reseptorejaan. tässä muodolla on  myös puolsutustehtävä,  johon alla oleva artikkeli keskittyy. S1P:n normaali määrä ei ole suuri. Tutkimus osoitti että MSC:t  voivat  vaikuttaa moninaisiin  S1P:iin  liittyviin  geeneihin samanaikaisesti.  Jos  MSC  käytettiin S1P:n ohella  geenivaiktuus oli muutakin kuin vain superpositiota toistensa suhteen, vaan merkitsevämpää tulosta  saatiin.

https://www.ncbi.nlm.nih.gov/pubmed/27994962

PeerJ. 2016 Dec 13;4:e2712. eCollection 2016.

 S1P resptorien säätely ja sfingosiinikinaasien (SphK)  expression säätely akuutissa  keuhkoendoteelisoluvauriossa 

S1P kykenee lisäämään endoteelisolubarrierin vastustuskykyä, resistenssiä. Fysiologisissa pitoisuuksissaan tämä S1P pitää yllä endoteelista barrierifunktiota. Mesenkymaalisten solujen  proliferaatiolla, regeneraatiolla ja  anti-inflamamtorisella aktiivisuudella  näyttää olevan mahdollista säädellä S1P:n homeostaattista kontrollia.  Mesenkymaaliset solut vaikuttivat S1P reseptorien lisääntymsitä , S1P:n pitoisuuden homeostaattisen kontrollin paranemista ja S1P:n metabolisten entsyymien ilmenemistä.

Tutkimus vahvistaa kokemusperäisen pohjan jatkotutkimuksille, joissa  selvitetään  keuhkovaurion endoteelibarrierifunktion kohentamisen tehokkuutta käyttämällä MSC kombinaationa sfingosiini1-fosfaatin kanssa ja  samalla selvitetään niiden mahdollsita synergististä mekanismia. 

KOMMENTTINI:  normaalituote metaboliassa S1P lienee myös molekyyli joka antaa  taaksepäin feed backia   sfinganiini-sfingosiini synteesinopeuteen tässä rondellissa. ja sitä ei voi yksinään  tutkia , hoitaa ja selvittää ottamatta huomioon  sytneesitien haarat. vauriossa  ilemisesti tulee olemaan putetta kaiksita valmiista tuotteista lokaalisesti.  Surfaktanttiavussa annetaan mm dipalmitaatteja,

( niitä käyttää nanotekniikkakin http://www.futuremedicine.com/doi/abs/10.2217/nnm.11.167?src=recsys&journalCode=nnm,  jos ei kaikki hyvksy possun  lipideistä tehtyjä surfaktanttteja hengenpelastukseensa)

Kehon plmitiinihaposta  kondensoituu  aktivoidun seriinin aknssa   ketosfinganiinia (Sa) , josta  tulee sfingosiinia (So), keramideja jne, mutta  myös  suoraakin tietä voi fosforyloitua  S1P-molekyyliä, ksoka sillä on "oma tehtävä" ilm. tuo barrierein vahvistus, eikä vain membraanilipiditehtävä sfingomyeliinina tai keramidijohdoksina, sulfatideina ym) -tässä pitää tarkistaa  rondelli.  1.4. 2017

LÄHDE:  Regulation of S1P receptors and sphingosine kinases expression in acute pulmonary endothelial cell injury. Liu H¹, Zhang Z¹, Li P¹, Yuan X¹, Zheng J¹, Liu J², Bai C¹, Niu W¹.

Abstract

BACKGROUND:

Acute lung injury and acute respiratory distress syndrome (ALI/ARDS) is a severe clinical syndrome with mortality rate as high as 30-40%. There is no treatment yet to improve pulmonary endothelial barrier function in patients with severe pulmonary edema. Developing therapies to protect endothelial barrier integrity and stabilizing gas exchange is getting more and more attention.
Sphingosine-1-phosphate (S1P) is able to enhance the resistance of endothelial cell barrier. S1P at physiological concentrations plays an important role in maintaining endothelial barrier function. Proliferation, regeneration and anti-inflammatory activity that mesenchymal stem cells (MSCs) exhibit make it possible to regulate the homeostatic control of S1P.

METHODS: By building a pulmonary endothelial cell model of acute injury, we investigated the regulation of S1P receptors and sphingosine kinases expression by MSCs during the treatment of acute lung injury using RT-PCR, and investigated the HPAECs Micro-electronics impedance using Real Time Cellular Analysis.

RESULTS: It was found that the down-regulation of TNF-α expression was more significant when MSC was used in combination with S1P. The combination effection mainly worked on S1PR2, S1PR3 and SphK2. The results show that when MSCs were used in combination with S1P, the selectivity of S1P receptors was increased and the homeostatic control of S1P concentration was improved through regulation of expression of S1P metabolic enzymes.

DISCUSSIONS: The study found that, as a potential treatment, MSCs could work on multiple S1P related genes simultaneously. When it was used in combination with S1P, the expression regulation result of related genes was not simply the superposition of each other, but more significant outcome was obtained. This study establishes the experimental basis for further exploring the efficacy of improving endothelial barrier function in acute lung injury, using MSCs in combination with S1P and their possible synergistic mechanism.

KEYWORDS:

Acute pulmonary endothelial cell injury; Mesenchymal stem cells; S1p receptors; Sphingosine-1-phosphate

PMID:

27994962

PMCID:

PMC5157198

DOI:

10.7717/peerj.2712

Free PMC Article

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