Rescue of TNFα‐inhibited neuronal cells by IGF‐1 involves Akt and c‐Jun N‐terminal kinases

Prashanth, K; Yadav, Ajay; Singh, G.; Nandana, Srinivas; Banerjee, Kakoli

doi:10.1002/jnr.20081

Cited by 44 publications

(36 citation statements)

References 36 publications

(50 reference statements)

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“…PKB has previously been implicated in the signalling pathways of IL-1β and TNF-α [39,40]. Consistent with such a mechanism of action, the overexpression of kinase-dead PKB enhanced cytokine-induced apoptosis and necrosis, whereas constitutively-active PKB diminished these effects.…”

Section: Discussionmentioning

confidence: 56%

Glucagon-like peptide-1 protects beta cells from cytokine-induced apoptosis and necrosis: role of protein kinase B

et al. 2005

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Aims/hypothesis: The gut hormone glucagonlike peptide-1 (GLP-1) decreases beta cell apoptosis in a protein kinase B (PKB)-dependent fashion, and increases islet cell mass and function in vivo. In contrast, cytokines induce beta cell apoptosis, leading to decreased islet mass and type 1 diabetes. In the present study we used rat INS-1E beta cells and primary rat islet cells to examine the potential role of PKB as a mediator of the effect of GLP-1 on cytokine-induced apoptosis. Methods: Cell viability was determined by MTTassay, and apoptosis and necrosis by Hoechst 33342-propidium iodide staining. Immunoblot analysis was used to detect changes in protein expression, including active (phosphorylated) and total PKB, phosphorylated and total glycogen synthase kinase-3β, activated caspase-3 and inducible nitric oxide synthase. Reactive oxygen species were determined by 1,7-dichlorofluorescein (DCF) analysis, and mutant forms of PKB were introduced into cells using adenoviral vectors. Results: Incubation of INS-1E cells with cytokines (IL-1β, TNF-α and interferon-γ; 10-50 ng/ml) for 18 h significantly decreased cell viability (by 44%, p<0.001), cell proliferation (by 80%, p<0.001), and activation of PKB (by 67%, p<0.001). Pre-treatment with exendin-4 (10 −7 mol/l), a long-acting GLP-1 receptor agonist, partially protected the cells against cytokine-induced toxicity (p<0.01) in association with a reduction in cytokine-induced inhibition of PKB phosphorylation (p<0.05). Exendin-4 pre-treatment did not change cell proliferation. Cytokine treatment increased apoptosis (by 156%, p<0.05) and necrosis (from undetectable to 2.6% of cells). These increases were both reduced by pre-treatment with exendin-4 (p<0.05-0.01). Furthermore, cytokine-induced apoptosis and necrosis were significantly increased in cells infected with kinase-dead PKB (p<0.05), and the protective effect of exendin-4 on both parameters was fully abolished in these cells. Similar changes were observed in primary islet cells. In parallel with these changes, exendin-4 decreased the cytokine-induced activation of caspase-3 (by 46%, p<0.05), and decreased levels of inducible nitric oxide synthase (by 71%, p<0.05) and reactive oxygen species (by 27%, p< 0.05). Conclusions/interpretation: The results of our study indicate that GLP-1 plays a protective role against cytokineinduced apoptosis and necrosis in beta cells through a PKB-dependent signalling pathway.

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Section: Discussionmentioning

confidence: 56%

Glucagon-like peptide-1 protects beta cells from cytokine-induced apoptosis and necrosis: role of protein kinase B

et al. 2005

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“…We have previously shown that IGF-1 was involved in survival of neuronal cells via the JAK/STAT, PI3kinase, and JNK kinase pathways (12,13). However, as the target genes activated by IGF-1 in neuronal cells are not clear, we screened for various downstream molecules like BCL2, MYC, and cyclin D1 in neuronal cells following IGF-1 stimulation.…”

Section: Igf-1 Upregulates Cyclin D1 In Neuronal Cellsmentioning

confidence: 99%

“…IGF-1 has been shown to regulate cyclins, CDK protein expression, and retinoblastoma (Rb) protein phosphorylation in breast cancer cell lines (11). Our previous studies have shown that IGF-1 was a potent survival and rescue factor for dying neurons mediated by JAK/STAT, PI3kinase as well as JNK kinase pathway (12,13). However, the specific target genes involved in IGF-1 mediated cell survival in neuronal cells are not clear.…”

Section: Introductionmentioning

confidence: 99%

IGF‐1 stimulated upregulation of cyclin D1 is mediated via STAT5 signaling pathway in neuronal cells

et al. 2013

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Signal Transducer and Activator of Transcription (STATs) regulate various target genes such as cyclin D1, MYC, and BCL2 in nonneuronal cells which contribute towards progression as well as prevention of apoptosis and are involved in differentiation and cell survival. However, in neuronal cells, the role of STATs in the activation and regulation of these target genes and their signaling pathways are still not well established. In this study, a robust cyclin D1 expression was observed following IGF-1 stimulation in SY5Y cells as well as neurospheres. JAK/STAT pathway was shown to be involved in this upregulation. A detailed promoter analysis revealed that the specific STAT involved was STAT5, which acted as a positive regulatory element for cyclin D1 expression. Overexpression studies confirmed increase in cyclin D1 expression in response to STAT5a and STAT5b constructs when compared to dominantnegative STAT5. siRNA targeting STAT5, diminished the cyclin D1 expression, further confirming that STAT5 specifically regulated cyclin D1 in neuronal cells. Together, these findings shed new light on the mechanism of IGF-1 mediated upregulation of cyclin D1 expression in neural cell lines as well as in neural stem cells via the JAK/STAT5 signaling cascade.

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“…IGF-1 activates various signaling pathways that enhance cell survival and proliferation, including pathways mediated by PI3-kinase/Akt (Xu et al, 1999;Kenchappa et al, 2004) and mitogenactivated protein kinases (MAPKs) (Chow et al, IGF-1 (100 ng/ml) was added 30 min later, and the cells were incubated for 6 h before lysis, SDS-PAGE, and immunoblotting to detect ZNF143 expression. In (A), the inhibitors were PD98059 (10 μM), SB203580 (10 μM), 10 μM SP600125 (10 μM), and wortmannin (100 nM).…”

Section: Phosphatidylinositol-3-kinase (Pi3-kinase) and Nadph Oxidasementioning

confidence: 99%

IGF-1 induces expression of zinc-finger protein 143 in colon cancer cells through phosphatidylinositide 3-kinase and reactive oxygen species

Paek

Kim

et al. 2010

Exp Mol Med

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Expression of zinc-finger protein 143 (ZNF143), a human homolog of the Xenopus transcriptional activator protein Staf, is induced by various DNA-damaging agents including etoposide, doxorubicin, and γ-irradiation. ZNF143 binds to cisplatin-modified DNA, and its levels are increased in cancer cells that are resistant to anticancer drugs, including cisplatin, suggesting that it plays a role in carcinogenesis and cancer cell survival. However, the mechanism of ZNF143 induction in cancer cells remains unclear. Both insulin-like growth factor-1 (IGF-1) and its receptor (IGF-1R) have been reported to be overexpressed in cancer cells and to be related to anticancer drug resistance, but the identity of the relevant signaling mediators is still being investigated. In the present study, we observed that IGF-1 was able to induce ZNF143 expression in HCT116 human colon cancer cells and that wortmannin, an inhibitor of phosphatidylinositide 3-kinase (PI3-kinase), inhibited this induction, as did diphenyleneiodonium (DPI), an NADPH oxidase inhibitor, and monodansylcardavarine (MDC), a receptor internalization inhibitor. Treatment with MDC decreased the IGF-1-stimulated generation of reactive oxygen species. Taken together, these data suggest that IGF-1 induces ZNF143 expression in cancer cells via PI3-kinase and reactive oxygen species generation during receptor internalization.

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Rescue of TNFα‐inhibited neuronal cells by IGF‐1 involves Akt and c‐Jun N‐terminal kinases

Cited by 44 publications

References 36 publications

Glucagon-like peptide-1 protects beta cells from cytokine-induced apoptosis and necrosis: role of protein kinase B

Glucagon-like peptide-1 protects beta cells from cytokine-induced apoptosis and necrosis: role of protein kinase B

IGF‐1 stimulated upregulation of cyclin D1 is mediated via STAT5 signaling pathway in neuronal cells

IGF-1 induces expression of zinc-finger protein 143 in colon cancer cells through phosphatidylinositide 3-kinase and reactive oxygen species

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