Department of Surgical and Gastroenterological Sciences, University of Padua, Padua, Italy.
BMC Gastroenterol. 2010 Apr 1;10:35. doi: 10.1186/1471-230X-10-35.
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.
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.
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).
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.
Bax 抑制剂-1（BI-1）是一种进化上保守的内质网蛋白，当其在哺乳动物细胞中过表达时，可抑制 Bax（Bcl-2 家族的促凋亡成员）诱导的细胞凋亡。本研究的目的是：（1）阐明内在抗凋亡和促凋亡介质的作用，评估不同程度肝损伤患者肝组织中的 Bax 和 BI-1 mRNA 和蛋白表达；（2）确定 HCV 和 HBV 感染是否调节所述表达。
我们检查了 62 名患者：39 名慢性肝炎（CH）患者（31 名 HCV 相关，8 名 HBV 相关）；7 名肝硬化患者（6 名 HCV 相关，1 名 HBV 相关）；13 名肝细胞癌（HCC）患者[7 名在病毒性肝硬化（6 名 HCV-和 1 名 HBV-相关），6 名在非病毒性肝硬化]；和 3 名对照。通过实时 PCR 定量 Bax 和 BI-1 mRNA，通过 Western blot 定量 BI-1 蛋白表达。
CH 组织的 BI-1 mRNA 水平明显高于 HCC 周围的肝硬化组织（P < 0.0001）或 HCC（P < 0.0001）。HCV 基因型 1 相关的 CH 组织中 Bax 转录物显著高于 HCV 基因型 3 相关的 CH（P = 0.033）。在 CH 组织中观察到 BI-1 和 Bax 转录物之间呈正相关，即使在单独考虑 HCV 相关 CH 和 HCV 基因型 1 相关 CH 时也是如此（P = 0.0007、P = 0.0005 和 P = 0.0017）。
BI-1 的表达随着肝损伤的进展而下调。在早期肝病中观察到的高 BI-1 mRNA 水平可能使病毒感染的细胞免受凋亡，而其逐渐下调可能促进肝细胞癌的发生。HCV 基因型似乎在 Bax 转录物表达中具有重要作用。
