Peroxynitrite induces GADD34, 45, and 153 VIA p38 MAPK in human neuroblastoma SH-SY5Y cells

Oh‐hashi, Kentaro; Maruyama, Wakako; Isobe, Ken‐ichi

doi:10.1016/s0891-5849(00)00461-5

Cited by 118 publications

(87 citation statements)

References 38 publications

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“…Confirming this notion, gefitinib did cause a time-dependent dephosphorylation and transcriptional downregulation of ERK1/2 in NE tumour cells. In addition, we observed an upregulation of the growth arrest and DNA-damage inducible gene, GADD153, which is involved in G1/ G0 arrest (Wang and Ron, 1996;Oh-Hashi et al, 2001). The expression of GADD153 is known to be regulated by both ERK1/2 and p38 MAPK: While p38 MAPK stimulates the expression of GADD153, ERK1/2 inhibits the expression (Kultz et al, 1998;OhHashi et al, 2001).…”

Section: Discussionmentioning

confidence: 86%

A novel approach in the treatment of neuroendocrine gastrointestinal tumours. Targeting the epidermal growth factor receptor by gefitinib (ZD1839)

et al. 2003

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Therapeutic options to inhibit the growth and spread of neuroendocrine (NE) gastrointestinal tumours are still limited. Since gefitinib (4-(3-chloro-4-fluoroanilino)-7-methoxy-6-(3-morpholinopropoxy)quinazoline), an inhibitor of epidermal growth factor receptorsensitive tyrosine kinase (EGFR-TK), had been shown to suppress potently the growth of various non-NE tumour entities, we studied the antineoplastic potency of gefitinib in NE gastrointestinal tumour cells. In human insulinoma (CM) cells, in human pancreatic carcinoid (BON) cells and in NE tumour cells of the gut (STC-1), gefitinib induced a time-and dose-dependent growth inhibition by almost 100%. The antiproliferative potency of gefitinib correlated with the proliferation rate of the tumour cells. So the IC 50 value of gefitinib was 4.770.6 mM in the fast-growing CM cells, still 16.870.4 mM in the moderate-growing BON cells, and up to 31.572.5 mM in the slow-growing STC-1 cells. Similarly, the induction of apoptosis and cell-cycle arrest by gefitinib differed according to growth characteristics: fast-growing CM cells displayed a strong G0/G1 arrest in response to gefitinib, while no significant cell-cycle alterations were seen in the slow-growing STC-1. Vice versa, the proapoptotic effects of gefitinib, as determined by caspase-3 activation and DNA fragmentation, were most pronounced in the slow-growing STC-1 cells. Using cDNA microarrays, we found extensive changes in the expression of genes involved in the regulation of apoptosis and cell cycle after incubation with gefitinib. Among them, an upregulation of the growth arrest and DNA damage-inducible gene GADD153 was observed. Phosphorylation of ERK1/2, which inhibits GADD153 expression, was reduced in a time-dependent manner. However, no gefitinib-induced activation of the GADD153-inducing p38 mitogen-activated protein kinase was detected. Our data demonstrate that the inhibition of EGFR-TK by gefitinib induces growth inhibition, apoptosis and cell-cycle arrest in NE gastrointestinal tumour cells. Thus, EGFR-TK inhibition appears to be a promising novel approach for the treatment of NE tumour disease.

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Section: Discussionmentioning

confidence: 86%

A novel approach in the treatment of neuroendocrine gastrointestinal tumours. Targeting the epidermal growth factor receptor by gefitinib (ZD1839)

et al. 2003

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“…CHOP can be post-translationally activated by p38 MAPK through phosphorylation at Ser78 and Ser81 (Wang and Ron, 1996) and a p38 MAPK antagonist represses peroxynitrite-induced CHOP mRNA and protein expression (Oh-Hashi et al, 2001). Since CHOP induction has been linked to cell death following prolonged ER stress, the p38 MAPK pathway could paradoxically also induce the expression of cell death modulators after PDT.…”

Section: Discussionmentioning

confidence: 99%

Molecular effectors and modulators of hypericin-mediated cell death in bladder cancer cells

et al. 2007

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Photodynamic therapy (PDT) is an anticancer approach utilizing a light-absorbing molecule and visible light irradiation to generate, in the presence of O 2 , cytotoxic reactive oxygen species, which cause tumor ablation. Given that the photosensitizer hypericin is under consideration for PDT treatment of bladder cancer we used oligonucleotide microarrays in the T24 bladder cancer cell line to identify differentially expressed genes with therapeutic potential. This study reveals that the expression of several genes involved in various metabolic processes, stress-induced cell death, autophagy, proliferation, inflammation and carcinogenesis is strongly affected by PDT and pinpoints the coordinated induction of a cluster of genes involved in the unfolded protein response pathway after endoplasmic reticulum stress and in antioxidant response. Analysis of PDT-treated cells after p38 MAPK inhibition or silencing unraveled that the induction of an important subset of differentially expressed genes regulating growth and invasion, as well as adaptive mechanisms against oxidative stress, is governed by this stress-activated kinase. Moreover, p38 MAPK inhibition blocked autonomous regrowth and migration of cancer cells escaping PDT-induced cell death. This analysis identifies new molecular effectors of the cancer cell response to PDT opening attractive avenues to improve the therapeutic efficacy of hypericin-based PDT of bladder cancer.

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“…43 We infected SupT1 cells with pHR-VPR and harvested three time points at 24, 48, and 72 h post-infection, then assayed for the presence of activated, phosphorylated p38 kinase by Western blot. We found that, as we previously observed for JNK, p38 kinase was not activated in Vprexpressing cells (Figure 6b).…”

Section: Induction Of Apoptosis By Vpr Is Not Mediated By Activation mentioning

confidence: 99%

ATR and GADD45α mediate HIV-1 Vpr-induced apoptosis

et al. 2005

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The human immunodeficiency virus type-1 (HIV-1) accessory gene vpr encodes a conserved 96-amino-acid protein that is necessary and sufficient for the HIV-1-induced block of cellular proliferation. Expression of vpr in CD4 þ lymphocytes results in G 2 arrest, followed by apoptosis. In a previous study, we identified the ataxia telangiectasia-mutated (ATM) and Rad3-related protein (ATR) as a cellular factor that mediates Vpr-induced cell cycle arrest. In the present study, we report that the breast cancer-associated protein-1 (BRCA1), a known target of ATR, is activated in the presence of Vpr. In addition, the gene encoding the growth arrest and DNA damage-45 protein a (GADD45a), a known transcriptional target of BRCA1, is upregulated by Vpr in an ATRdependent manner. We demonstrate that RNAi-mediated silencing of either ATR or GADD45a leads to nearly complete suppression of the proapoptotic effect of Vpr. Our results support a model in which Vpr-induced apoptosis is mediated via ATR phosphorylation of BRCA1, and consequent upregulation of GADD45a.

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Peroxynitrite induces GADD34, 45, and 153 VIA p38 MAPK in human neuroblastoma SH-SY5Y cells

Cited by 118 publications

References 38 publications

A novel approach in the treatment of neuroendocrine gastrointestinal tumours. Targeting the epidermal growth factor receptor by gefitinib (ZD1839)

A novel approach in the treatment of neuroendocrine gastrointestinal tumours. Targeting the epidermal growth factor receptor by gefitinib (ZD1839)

Molecular effectors and modulators of hypericin-mediated cell death in bladder cancer cells

ATR and GADD45α mediate HIV-1 Vpr-induced apoptosis

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