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Title:Vpliv mleka, mlečnih bioaktivnih peptidov in l-arginina na celično signalizacijo v kožnih fibroblastih
Authors:Kocić, Hristina (Author)
Langerholc, Tomaž (Mentor) More about this mentor... New window
Files:.pdf DOK_Kocic_Hristina_2018.pdf (3,71 MB)
 
Language:Slovenian
Work type:Doctoral dissertation (mb31)
Organization:MF - Faculty of Medicine
Abstract:Danes imamo na trgu različne kozmetične izdelke, ki vsebujejo večinoma kravje mleko ali sirotko, šele v zadnjih letih pa so na trgu prisotni tudi izdelki, ki vsebujejo mleko. Njihov učinek se odraža v izboljšani vlažnosti in mehkobi kože z nežnim regenerativnim učinkom. Glede na to, da so polarni lipidi mleka v obliki stabilnih emulzij, lažje prodrejo v kožo in eksperimentalno se je pokazalo, da spodbujajo rast dlak. V študijah in vitro na kulturah fibroblastov kože, se je pokazal učinek kravjega mleka pri spodbujanju proliferacije celic v primerjavi s kontrolnimi celicami. Fibroblasti kože predstavljajo fenotipsko zelo dinamično raznovrstno populacijo, ki se nahaja v plasti dermisa. Signaliziranje poteka preko sprememb v izraženosti različnih membranskih receptorjev in proteinov v signalnih poteh, ki spreminjajo kinazno aktivnost, delovanje transkripcijskih faktorjev in modulatorjev apoptoze. Omenjeni mehanizmi so dobro preučeni v procesu celjenja ran in patoloških fibroz. Narejena študija je imela namen raziskati učinke različnih vrst mleka, bioaktivnih proteinov, peptidov in amino kisline L-arginin na metabolizem oz. signalizacijo fibroblastov kože. To predstavlja osnovo za razlago potencialno koristnih učinkov mleka v dermatologiji ter možnost njegove uporabe. Raziskovali smo tri področja: i) Raziskave na področju celične signalizacije fibroblastov pri izpostavitvi človeškemu, osličjemu ali kravjemu mleku in njihovim vrstno-specifičnim kolostrumom, komercialnim formulam mleka v prahu, -kazeinom, -kazomorfinom in L-argininu. Ta poskus naj bi dal odgovor na vprašanje, katera od omenjenih snovi kaže največji proliferativni, (proti)apoptotični in (proti)vnetni učinek v primerjavi s kontrolnimi celicami. Po izpostavitvi smo zasledovali jedrni transkripcijski faktor NF-κB p65, signalne molekule celične proliferacije (kinaze Akt-1, fosfo-Akt-1, Erk-1, fosfo-Erk-1, JNKa, fosfo-JNK in fosfo-STAT-1), faktor migracije (CD26) in proteine v notranji poti apoptoze (Bcl2 in Bax). Pridobljeni podatki so lahko začetna osnova za razumevanje njihove morebitne dermatološke uporabe; ii) Raziskave na področju praktične biotehnologije na podlagi opazovanja učinkov različnih vrst mleka, ki jih imajo na sproščanje ftalatov iz plastičnih mas in proučevanje možnosti enkapsuliranja osličjega mleka v nanoliposome; iii) praktična priprava kozmetičnih formulacij (krem) na osnovi nanoliposomov, v katere je enkapsulirano mleko in L-arginin. Glede na znižanje ravni NF-κB p65 v kožnih fibroblastih lahko zaključimo, da imata človeško in osličje mleko protivnetno delovanje. Glede na podatek, da sta intenzivno zvišanje NF-κB p65 pokazala β-kazein in β-kazomorfin-7, je možno, da ne-kazeinski proteini humanega in osličjega mleka pripomorejo k protivnetnim značilnostim. Aktivacija kinaz je bila opažena pri vzorcih mleka s kazeinom in L-argininom. To kaže na to, da so kazeinski proteini in L-arginin odgovorni za stimulacijo rasti celic in posledično za morebitno regeneracijo kože pri tretmaju z mlekom. Med vsemi obravnavanimi kinazami se je aktivna oblika Erk-kinaze večkratno povišala, kar nakazuje na možnost uporabe te kinaze kot specifičnega markerja za regenerativno-proliferativni potencial fibroblastov. Osličje mleko je primerjalno bolj občutljivo na onesnaženje s ftalati iz plastičnih mas, zato se je pri pakiranju potrebno izogibati plastični embalaži. Nanoliposomi predstavljajo ustrezen sistem za enkapsulacijo mleka. Njihova uporaba predvidoma omogoča boljši dostavni sistem proteinov za kožo.
Keywords:Fibroblasti kože, osličje mleko, beta-kazeinom, beta-kazomorfinom, L-arginin, transkripcijski faktor NF-κB p65, kinaze Akt-1, fosfo-Akt-1, Erk-1, fosfo-Erk-1, JNK, fosfo-JNK, fosfo-STAT-1, CD26, Bc2, Bax, ftalati, fosfolipidna nanosfera
Year of publishing:2018
Source:Maribor
COBISS_ID:297056256 Link is opened in a new window
NUK URN:URN:SI:UM:DK:UCN6RARH
Views:406
Downloads:30
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Categories:MF
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Secondary language

Language:English
Title:Effects of milk, milk-derived bioactive peptides and l-arginine on cell signalling in skin fibroblasts
Abstract:Identification and characterization of specific cell-signaling pathways may be valuable in developing therapeutic approaches to delay skin aging and to modulate immune and inflammatory reactions. In our thesis, skin fibroblasts (L929) cell culture line has been studied for the effects of milk bioactive peptides, measured by modulation of the signaling downstream effectors responsible for cell and tissue growth, apoptosis and immune function. In our study we hypothesized that donkey milk and milk from human and other species (e.g. cows), infant baby formulas, casein and -casomorphine-7 may have an influence on growth, apoptosis, and immune function of skin fibroblasts through the effects on growth-regulatory kinases (Akt-pAkt, Erk/pErk1/2, JNK/pJNK, pStat-1), inflammatory transcriptional factor NF-κB p65, cell surface antigen CD26 and Bcl-2/Bax ratio of skin fibroblasts. Down-regulation of the inflammatory NF-κB transcription factor p65 subunits was observed after the exposure of skin fibroblasts to donkey milk and human colostrum, while casein, -casomorphine-7 and cow milk exerted an opposite effect. Obtained results may suggest that non-casein bioactive peptides of donkey and human milk may be responsible for the anti-inflammatory properties of donkey and human milk. The exposure of skin fibroblasts to all examined milk species and -casein led to the activation of growth-regulatory kinases (Akt1/2/3 kinase, Erk kinase, and JNK kinase), especially the p-Erk pathway, which may suggest that essential amino acids of casein may be responsible for Erk-induced cell cycle activation and proliferation. The opposite effect was observed when cells were exposed to β-casomorphine-7, which may affect the survival of skin fibroblasts and their proliferative potential. Exposure of skin fibroblasts to human milk significantly upregulated Bcl2. Since a semi-essential amino acid L-arginine may be of fundamental importance in various intracellular and intercellular pathways related to skin repair and facilitated wound healing, our study found that exposure of skin fibroblasts to L-arginine may help to maintain and stimulate proliferative potential (through the activation of Erk, pErk, JNK and pJNK kinases), anti-apoptotic potential (through the increase of Bcl-2/Bax ratio) and increased immune defense and inflammatory potential (through the increase of NF-κB p65). Finally, our results have shown that donkey milk may be useful in achieving anti-aging effects in regenerative and aesthetic dermatology, especially when encapsulated in nanoliposomes. Donkey milk has been shown to be the most susceptible to phthalate liberation from plastic. In order to decrease potential phthalate liberation, dermatological products containing donkey milk should be packaged in glass containers.
Keywords:skin fibroblasts, donkey milk, beta-casein, beta-casomorphine, L-arginin, transcription factor NF-κB p65, kinases Akt-1, phospho-Akt-1, Erk-1, phospho-Erk-1, JNK, phospho-JNK, phospho-STAT-1, CD26, Bc2, Bax, phthalathes, phospholipid nanosphere


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