Dataset Information

The role of NF-{kappa}B-1 and NF-{kappa}B-2-mediated resistance to apoptosis in lymphomas.

ABSTRACT: The NF-kappaB pathways have been implicated in tumorigenesis in several lymphoid malignancies, including non-Hodgkin's and Hodgkin's lymphomas. However, the antiapoptotic functions and the mechanism responsible for signaling through each NF-kappaB pathway remain to be elucidated. In the current study, lymphoma cell lines with constitutively active NF-kappaB were found to be resistant to inducers of the extrinsic and intrinsic apoptosis pathways. Resistance to cell death resulted from blocks early and late in the apoptosis cascade. Several NF-kappaB target genes were overexpressed in these cell lines, including Bcl-xL, Fas-associated death domain-like IL-1beta-converting enzyme inhibitor protein, cellular inhibitor of apoptosis, and X inhibitor of apoptosis. Inhibition of the canonical or noncanonical NF-kappaB pathways with small interfering RNAs or adenovirus expressing a stable form of inhibitor of NF-kappaB (IkappaB) enhanced sensitivity to apoptosis inducers and resulted in lower levels of Bcl-xL or Fas-associated death domain-like IL-1beta-converting enzyme inhibitor protein, cellular inhibitor of apoptosis, and X inhibitor of apoptosis. These findings demonstrate an important role of both NF-kappaB pathways in mediating resistance to apoptosis and distinctive antiapoptotic downstream target gene profiles responsible for this effect.

SUBMITTER: Bernal-Mizrachi L

PROVIDER: S-EPMC1482593 | biostudies-literature | 2006 Jun

REPOSITORIES: biostudies-literature

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The role of NF-{kappa}B-1 and NF-{kappa}B-2-mediated resistance to apoptosis in lymphomas.

Bernal-Mizrachi Leon L Lovly Christine M CM Ratner Lee L

Proceedings of the National Academy of Sciences of the United States of America 20060602 24

The NF-kappaB pathways have been implicated in tumorigenesis in several lymphoid malignancies, including non-Hodgkin's and Hodgkin's lymphomas. However, the antiapoptotic functions and the mechanism responsible for signaling through each NF-kappaB pathway remain to be elucidated. In the current study, lymphoma cell lines with constitutively active NF-kappaB were found to be resistant to inducers of the extrinsic and intrinsic apoptosis pathways. Resistance to cell death resulted from blocks earl ...[more]

PMID: 16751281

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Project description:Clinical application of gentamicin (GM) is well known to be associated with the development of acute kidney injury (AKI). This study was the first to investigate the possible protective effects of D-limonene (D-lim) on AKI following GM administration in rats. 32 rats arranged in four groups (n = 8): (1) the control group received saline intraperitoneally (0.5 ml/day) and orally (0.5 ml/day), (2) the D-lim group received D-lim (100 mg/kg) orally and saline (0.5 ml/day) intraperitoneally, (3) the GM group received GM (100 mg/kg/day) intraperitoneally and saline (0.5 ml/day) orally, and (4) the treated group received intraperitoneal GM (100 mg/kg) and oral D-lim (100 mg/kg). All treatments were performed daily for 12 consecutive days. Results revealed that D-lim ameliorated GM-induced AKI, oxidative stress, mitochondrial apoptosis, and inflammation. D-lim showed nephroprotective effects as reflected by the decrease in serum urea and creatinine and improvement of renal histopathological changes. D-lim alleviated GM-induced oxidative stress by increasing the activities of renal catalase, serum and renal glutathione peroxidase, and renal superoxide dismutase and decreasing renal malondialdehyde and serum nitric oxide levels. Intriguingly, D-lim suppressed mitochondrial apoptosis by considerably downregulating Bax and caspase-3 (Casp-3) mRNA and protein expressions and markedly enhancing Bcl2 mRNA and protein expressions. Furthermore, D-lim significantly decreases GM-induced inflammatory response through downregulation of NF-κB, IL-6, and TNF-α mRNA and/or protein expressions and decrease in renal myeloperoxidase activity. Finally, D-lim remarkably downregulated PCNA protein expression in the treated group compared with the GM group. In brief, this study showed that D-lim alleviated AKI following GM administration in rats, partially through its antioxidant, anti-inflammatory, and antiapoptotic activities as well as downregulation of PCNA expression.

Dataset Information

The role of NF-{kappa}B-1 and NF-{kappa}B-2-mediated resistance to apoptosis in lymphomas.

Publications

The role of NF-{kappa}B-1 and NF-{kappa}B-2-mediated resistance to apoptosis in lymphomas.

Similar Datasets

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