title: In vivo up-regulation of the unfolded protein response after hypoxia.
abstract: BACKGROUND
  Low oxygen (O2) availability, a condition called hypoxia, has different and profound consequences in tissues and organs. Besides the hypoxia-inducible response, mammalian cells induce a coordinated cytoprotective pathway called Unfolded Protein Response (UPR). We studied the molecular basis of UPR and apoptosis in animal models exposed to different hypoxic stresses and assessed the ability of liver and myocardium to respond to low oxygen by activating different arms of the UPR according to the severity of the insults in a tissue specific manner.
  
  
  METHODS
  We assessed the levels of several UPR markers in hypoxic animals by Real Time PCR and Western blotting.
  
  
  RESULTS
  While the hepatocytes activate the apoptotic pathway mediated, in part, by CHOP and p-JNK, we could not detect an UPR-dependent apoptosis in myocytes. Moreover, severe hypoxia results in ATF4 translation, and induction of CHOP and GADD34 transcripts in liver, by contrast in the myocardium, the ATF4-CHOP-GADD34 signaling pathway is not detectably activated.
  
  
  CONCLUSIONS
  Comparison of several UPR markers in liver and myocardium enabled to underscore the ability of hepatocytes and myocites to selectively activate and fine tune the UPR signaling pathway during hypoxia in vivo.
authors.affiliation: Department of Medicine, Surgery and Dentistry, University of Milan, San Paolo Hospital, Milan, Italy. Tagliavacca.Luigina@hsr.it
authors.forename: Luigina
authors.initials: L
authors.lastname: Tagliavacca
authors.forename: Anna
authors.initials: A
authors.lastname: Caretti
authors.forename: Paola
authors.initials: P
authors.lastname: Bianciardi
authors.forename: Michele
authors.initials: M
authors.lastname: Samaja
mesh_terms: D051701:Activating Transcription Factor 4 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D015415:Biomarkers / Q000378:metabolism*; D015153:Blotting, Western; D002478:Cells, Cultured; D000860:Hypoxia / Q000503:physiopathology*; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D048670:MAP Kinase Kinase 4 / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D010766:Phosphorylation; D017510:Protein Folding; D054645:Protein Phosphatase 1 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D051742:Transcription Factor CHOP / Q000235:genetics / Q000378:metabolism; D056811:Unfolded Protein Response / Q000502:physiology*; D015854:Up-Regulation
chemical_list: C081452:Atf4 protein, mouse; D015415:Biomarkers; C497250:Ddit3 protein, mouse; D012333:RNA, Messenger; D051701:Activating Transcription Factor 4; D051742:Transcription Factor CHOP; D048670:MAP Kinase Kinase 4; C513256:Ppp1r15a protein, mouse; D054645:Protein Phosphatase 1