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Bax inhibitor-1 down-regulation in the progression of chronic liver diseases.
- Source :
-
BMC gastroenterology [BMC Gastroenterol] 2010 Apr 01; Vol. 10, pp. 35. Date of Electronic Publication: 2010 Apr 01. - Publication Year :
- 2010
-
Abstract
- Background: Bax inhibitor-1 (BI-1) is an evolutionary conserved endoplasmic reticulum protein that, when overexpressed in mammalian cells, suppresses the apoptosis induced by Bax, a pro-apoptotic member of the Bcl-2 family. The aims of this study were: (1) to clarify the role of intrinsic anti- and pro-apoptotic mediators, evaluating Bax and BI-1 mRNA and protein expressions in liver tissues from patients with different degrees of liver damage; (2) to determine whether HCV and HBV infections modulate said expression.<br />Methods: We examined 62 patients: 39 with chronic hepatitis (CH) (31 HCV-related and 8 HBV-related); 7 with cirrhosis (6 HCV-related and 1 HBV-related); 13 with hepatocellular carcinoma (HCC) [7 in viral cirrhosis (6 HCV- and 1 HBV-related), 6 in non-viral cirrhosis]; and 3 controls. Bax and BI-1 mRNAs were quantified by real-time PCR, and BI-1 protein expression by Western blot.<br />Results: CH tissues expressed significantly higher BI-1 mRNA levels than cirrhotic tissues surrounding HCC (P < 0.0001) or HCC (P < 0.0001). Significantly higher Bax transcripts were observed in HCV-genotype-1-related than in HCV-genotype-3-related CH (P = 0.033). A positive correlation emerged between BI-1 and Bax transcripts in CH tissues, even when HCV-related CH and HCV-genotype-1-related CH were considered alone (P = 0.0007, P = 0.0005 and P = 0.0017, respectively).<br />Conclusions: BI-1 expression is down-regulated as liver damage progresses. The high BI-1 mRNAs levels observed in early liver disease may protect virus-infected cells against apoptosis, while their progressive downregulation may facilitate hepatocellular carcinogenesis. HCV genotype seems to have a relevant role in Bax transcript expression.
- Subjects :
- Adult
Aged
Apoptosis Regulatory Proteins biosynthesis
Biopsy
Blotting, Western
Disease Progression
Female
Hepatitis C, Chronic metabolism
Hepatitis C, Chronic pathology
Humans
Liver pathology
Liver Cirrhosis metabolism
Liver Cirrhosis pathology
Male
Membrane Proteins biosynthesis
Middle Aged
Polymerase Chain Reaction
Prognosis
Young Adult
Apoptosis Regulatory Proteins genetics
Down-Regulation
Hepatitis C, Chronic genetics
Liver metabolism
Liver Cirrhosis genetics
Membrane Proteins genetics
RNA genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1471-230X
- Volume :
- 10
- Database :
- MEDLINE
- Journal :
- BMC gastroenterology
- Publication Type :
- Academic Journal
- Accession number :
- 20359348
- Full Text :
- https://doi.org/10.1186/1471-230X-10-35