having said that, K18 Gly mcehad smar njury whecompared to notransgenc andhK18 WT mce just after Fas alone njectoor MLR.These final results ndcate that K18 Gly mce are selectvely andhghly susceptble to specfc PP242 molecular weight varieties of apoptoss assocated njury.The ncreased lethalty K18 Gly mce was lkely due to mult orgafaure snce a number of abdomnal organs had been obviously paler K18 Gly versus K18 WT mce.These fndngs have been confrmed byhstologcal analyss whch showed extensve lverhemorrhage and cell drooff, pancreatc edema and slet cell necross K18 Gly anmals.Also, there was sgnfcanthepatc steatoss and glycogedepletoK18 Gly mce as confrmed by o red O and perodc acd Schff stanng, respectvely.Pancreatc endocrne injury was corroborated through the dramatcally decreased nsulstanng and reduced serum nsulK18 Gly pancreata.
The predspostoto STZ medated pancreatc damage s not associated with dfferences glucose or nsultolerance.Collectvely, these fndngs ndcate that the dramatc STZ medated njury K18 Gly mce s not related to selectve glucosehomeostass alterations but to generalzed epthelal tssue njury quite a few K18 expressng organs.We examned the cause of cell death K18 Gly mce.No result olver and pancreas keratfament JAK2 inhibitor organzatounder basal condtons was mentioned, but mmunostanng of K18 Gly lver and pancreas after STZ showed dramatc ncreased K18 apoptotc fragment formatoand even more promnent K8 S80 phosphorylatoas in contrast wth K18 WT tssues.ncreased apoptoss K18 Gly tssues was supported by blottng wth antbodes to cleaved caspase three as well as the K18 apoptotc fragment.
hence, the lver njury nvolves extensve apoptoss whe the pancreatc njury ncludes lmted apoptoss whch s consstent wth expermental pancreatts designs wherever apoptoss s typcally nversely

proportonal towards the severty of pancreatts33.K18 Gly predsposes transgenc mce to PUGNAc Fas nduced njury The protectve purpose of K18 glycosylatos additional confrmed by usng a extra selectve O GlcNAcase nhbtor, PUGNAc29, combned wth Fas antbody.We frst tested varous doses of PUGNAc nontransgenc mce gvethat the impact of PUGNAc s not well studed mce.Despite the fact that all mce appeared ordinary andhad no lver injury, PUGNAc caused lver accumulatoof O GlcNAc protens.Fas antbody admnstrato2 days immediately after PUGNAc treatment showed the K18 Gly mce are sgnfcantly more susceptble to lethalty as compared wth controls.PUGNAc Fas phenocopes the severe lverhemorrhage, apoptoss,hepatc steatoss and glycogedepletoseewth STZ.Gvethat the K18 Gly mutatohas no addtonal impact oFas alone medated lver njury, the phenotype of K18 Gly mce immediately after PUGNAc Fas admnstratos lkely linked to the accumulatoof O GlcNAc protens after PUGNAc treatment.K18 Gly alters proteknase phosphorylatomousehepatocyte prmary cultures handled wth STZ The phosphonostde three knase pathway s central tohepatc glucose, lpd and nsulmetabolsm34.