Clusterin (CLU) is a multifunctional glycoprotein that has secretory and nuclear isoforms. The two isoforms are known to play opposite roles in cell survival/death. In this review, we summarize recent progress on the pro-apoptotic function of nuclear CLU in vitro and in vivo and discuss previous reports on the role of CLU in brain damage and neurodegeneration.

The molecular mechanisms of pulmonary fibrosis are poorly understood. Previous reports indicate that activation of TGF-beta1 is essential for the development of pulmonary fibrosis. Here, we report that the proapoptotic Bcl-2 family member Bid is required for the development of pulmonary fibrosis after the intratracheal instillation of bleomycin. Mice lacking Bid exhibited significantly less pul...

Both anti- and proapoptotic activities have been reported to occur during chlamydial infection. To reconcile the apparent controversy, we compared host cell apoptotic responses to infection with 17 different chlamydial serovars and strains. None of the serovars caused any biologically significant apoptosis in the infected host cells. Host cells in chlamydia-infected cultures can continue to und...

We have previously correlated Chlamydia trachomatis antiapoptotic activity with the blockade of mitochondrial cytochrome c release and the inhibition of Bax and Bak activation. We now report that C. trachomatis infection leads to degradation of Bik, Puma, and Bim, three upstream proapoptotic BH3-only proteins of the Bcl-2 family that can transmit death signals to mitochondria by inhibiting the ...

The mechanisms that control cellular proliferation, as well as those related with programmed cell death or apoptosis, require precise regulation systems to prevent diseases such as cancer. Events related to cellular proliferation as well as those associated with apoptosis involve the regulation of gene expression carried out by three basic genetic expression regulation mechanisms: transcription...

OBJECTIVE Curcumin (diferuloylmethane) is a yellow-colored polyphenol with antiproliferative and proapoptotic activities to various types of cancer cells. This study explored the mechanism by which curcumin induces p53-null hepatoma cell apoptosis. RESULTS AKT, FOXO1, and FOXO3 proteins were downregulated after curcumin treatment. Conversely, PTEN was upregulated. Subcellular fractionations r...

Targeted gene disruption studies have established that the c-Jun NH(2)-terminal kinase (JNK) signaling pathway is required for stress-induced release of mitochondrial cytochrome c and apoptosis. Here we demonstrate that activated JNK is sufficient to induce rapid cytochrome c release and apoptosis. However, activated JNK fails to cause death in cells deficient of members of the Bax subfamily of...

In the present paper, we describe proapoptotic activity of several heterocyclic compounds 9, 12, 18, 19 and 20 possessing succinimide (as well as succinimide related) moieties. The compounds properties were examined with the aid of flow cytometry on the promyelocytic leukemia cell line HL-60. The highest proapoptotic activity exhibited compound 12 (4-{4-[4-(2-methoxyphenyl)piperazin-1-yl]butyl}...

One of the most promising strategies in cancer gene therapy is adenoviral transfer of proapoptotic genes. We therefore evaluated the novel strategy of adenovirally overexpressing the proapoptotic Bak gene. Our results showed marked apoptosis in cancer cells in vivo and in vitro after Bak gene transfer via a binary adenoviral vector system. This effect was not seen in a caspase 3-defective cell ...

Livin is a member of the inhibitors of apoptosis protein gene family, which is highly expressed in a variety of human neoplasms. Several studies have shown that down-regulation of Livin expression increases the apoptotic rate, reduces tumor growth potential, and sensitizes tumor cells to chemotherapeutic drugs. Furthermore, emerging data reveal that Livin fragments cleavaged by caspases restore...