title: Hepatocyte nuclear factor-1alpha mediated upregulation of albumin expression in focal ischemic rat brain.
abstract: OBJECTIVE
  Exogenous human albumin has been shown to be neuroprotective in experimental ischemic stroke and it is currently investigated in clinical trials. However, the role of endogenous expression of albumin and its transcriptional regulation in the ischemic  brain is not known. We have previously reported the upregulation of de novo synthesis of albumin in the ischemic rat brain (at 0 and 22 hours of reperfusion after 2 hours of ischemia). In this study, we analyzed the role of transcription factors in albumin expression in ischemic rat  brain.
  
  
  METHODS
  The putative transcription factor binding sites for the albumin promoter was analyzed using transcription factor search computational tool and validated in rat middle cerebral artery occlusion model of transient cerebral ischemia.
  
  
  RESULTS
  Computational  analysis predicted approximately 20 transcription factor binding sites including hepatocyte nuclear factor-1alpha (HNF-1alpha). We found for the first time mRNA and protein expression of HNF-1alpha in the control and ischemic rat brain. There was no significant difference in mRNA and protein  expression of HNF-1alpha between control and ischemic (0, 2 and 22 hours of reperfusion) group but there was increased interaction of HNF-1alpha with p300 (known interacting partner for HNF-1alpha, a histone acetyl-transferase) in 0- and 22-hour reperfusion groups. Also albumin promoter binding  activity of HNF-1alpha in ischemic animals of 0- and 22-hour reperfusion groups significantly increased compared to respective control group animals.
  
  
  CONCLUSIONS
  Although, HNF-1alpha is mainly expressed in the rat liver and involved in hepatic expression of albumin, our study conclusively  shows for the first time de novo synthesis of HNF-1alpha in rat brain. Moreover, an increased interaction of HNF-1alpha with p300 and albumin promoter seems to be responsible for overexpression of albumin in ischemic conditions.
authors.affiliation: Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Sector-67, S.A.S. Nagar, Punjab, India.
authors.forename: Kanaiyalal D
authors.initials: KD
authors.lastname: Prajapati
authors.forename: Shyam S
authors.initials: SS
authors.lastname: Sharma
authors.forename: Nilanjan
authors.initials: N
authors.lastname: Roy
mesh_terms: D000418:Albumins / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002545:Brain Ischemia / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000502:physiology; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation / Q000502:physiology; D015854:Up-Regulation; D050880:p300-CBP Transcription Factors / Q000235:genetics / Q000378:metabolism; D000099224:p300-CBP-Associated Factor
chemical_list: D000418:Albumins; D004268:DNA-Binding Proteins; D051538:Hepatocyte Nuclear Factor 1-alpha; D012333:RNA, Messenger; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor