Usporedba pentadekapeptida BPC 157 i Rac 1 inhibitora

master's thesis

• Title (english): Pentadecapeptide BPC 157 and Rac 1 inhibitors
• Author: Tinka Vidović
• Mentor: Predrag Sikirić (mentor)
• Committee member: Sven Seiwerth (predsjednik povjerenstva)
• Committee member: Jasenka Markeljević (član povjerenstva)
• Committee member: Predrag Sikirić (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Pharmacology); Zagreb
• Defense date and country: 2016-07-15, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Basic Medical Sciences; Pharmacology

Abstract

UVOD: Rac1 je mali signalizirajući G-protein koji može aktivirati NF-kappaB. Pentadekapeptid BPC 157 smanjuje transkripciju Vcam-1 u NF-kappaB signalnom putu kao i neki NF-kappaB inhibitori te suprimira da ERK inducira Vcam-1 preko NF-kappaB aktivacije. Pentadekapeptid BPC 157 može biti Rac1 aktivator ili inhibitor, te bi to moglo ovisiti o mjestu fosforilacije FAK/paksilin signalnog puta.
METODE: Pregled učinaka pentadekapeptida BPC 157 i Rac1 inhibitora na tumorski rast, ishemijsko-reperfuzijske ozljede, ulcerozni kolitis, virusne infekcije, multiplu sklerozu, depresiju i cijeljenje te usporedba sa učincima NF-kappaB inhibitora.
REZULTATI: Pentadekapeptid BPC 157 bi mogao biti novi NF-kappaB inhibitor. Dok je većina istraživanja o Rac1 inhibitorima napravljena na modelima inhibicije tumorskog rasta gdje je pronađena prekomjerna ekspresija Rac1, BPC 157 je najviše istraživan u modelima upalnih bolesti i cijeljenja. Transkripcijski faktor NF-kappaB povezuje upalne bolesti i tumore, te je moguće da je NF-kappaB signalni put poveznica između pentadekapeptida BPC 157 i Rac1 inhibitora. Pentadekapeptid BPC 157 i NF-kappaB inhibitori pozitivno utječu na sve navedene modele, dok Rac1 inhibitori nisu učinkoviti u modelima cijeljenja i depresije.
ZAKLJUČAK: Postoji mogućnost da je transkripcijski faktor NF-kappaB uzrok sličnosti između pentadekapeptida BPC 157 i Rac1 inhibitora u nekim modelima. Treba uzeti u obzir i druge signalne puteve kao što su CREB i ERK te da je moguće da je učinak BPC 157, kao i Rac1 inhibitora na te puteve stanično-specifičan.

Abstract (english)

BACKGROUND: Rac 1 is a small G-protein which can activate NF-kappaB. Pentadecapeptide BPC 157 decreases transcription of Vcam1 in NF-kappaB signalling pathway like some NF-kappaB inhibitors and supresses ERK induction of Vcam1 through NF-kappaB activation. Pentadecapeptide BPC 157 can be Rac1 activator or inhibitor, and that could depend on phosphorylation site of FAK/Paxillin pathway.
METHODS: Review of pentadecapeptide BPC 157 and Rac1 inhibitor effects on tumour growth, ischemia-reperfusion injuries, ulcerative colitis, viral infections, multiple sclerosis, depression and healing, as well as comparison with the effects of NF-kappaB inhibitors.
RESULTS: Pentadecapeptide BPC 157 could be a novel NF-kappaB inhibitor. While most of the research on Rac1 inhibitors is done in models of tumour growth inhibition where Rac1 overexpression is found, the research on BPC 157 is focused on inflammation diseases and healing. The NF-kappaB transcription factor is a link between inflammation and cancer, so it is possible that NF-kappaB pathway is a connection between pentadecapeptide BPC 157 and Rac1 inhibitors. Pentadecapeptide BPC 157 and NF-kappaB inhibitors have positive result in all of the models reviewed, while Rac1 inhibition is not affective in models of healing and depression.
CONCLUSION: It is possible that the NF-kappaB transcription factor is a cause of the similirality between BPC 157 and Rac1 inhibitors in some of the models. Other signalling pathways , like ERK and CREB must be considered, as well as the fact the effect of BPC 157 and Rac1 inhibitors on NF-kappaB could be cell specific.

• Keywords: pentadekapeptid BPC 157; rac1 inhibitori; NF-kappaB inhibitori
• Keywords (english): pentadecapeptide BPC 157; rac1 inhibitors; NF-kappaB inhibitors
• Language: croatian
• URN:NBN: urn:nbn:hr:105:415950
• Study programme: Title: Medicine; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2017-07-12 11:55:17