Bax inhibitor-1 down-regulation in the progression of chronic liver diseases

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.

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.

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).

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2010

Erschienen:

2010

Enthalten in:

Zur Gesamtaufnahme - volume:10

Enthalten in:

BMC gastroenterology - 10(2010) vom: 01. Apr., Seite 35

Sprache:

Englisch

Beteiligte Personen:

Kotsafti, Andromachi [VerfasserIn]
Farinati, Fabio [VerfasserIn]
Cardin, Romilda [VerfasserIn]
Burra, Patrizia [VerfasserIn]
Bortolami, Marina [VerfasserIn]

Links:

Volltext

Themen:

63231-63-0
Apoptosis Regulatory Proteins
Comparative Study
Journal Article
Membrane Proteins
RNA
Research Support, Non-U.S. Gov't
TMBIM6 protein, human

Anmerkungen:

Date Completed 15.07.2010

Date Revised 20.10.2021

published: Electronic

Citation Status MEDLINE

doi:

10.1186/1471-230X-10-35

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM197039448