Nitric oxide-mediated activation of extracellular signal-regulated kinase (erk) and c-jun n-terminal kinase (jnk) during hypoxia in cerebral cortical nuclei of newborn piglets

Mishra, Om P.; Zubrow, Alan B.; Ashraf, Qazi M.

doi:10.1016/j.neuroscience.2003.08.008

Cited by 43 publications

(39 citation statements)

References 59 publications

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“…JNK1 activity is suppressed after nitrosylation on Cys 116 of JNK1 by nitric oxide generated after IFN-␥ administration in macrophages (33). Conversely, nitric oxide mediates ERK and JNK activation during hypoxia in neuronal cells (34) and increases nitrosylation and phosphorylation of JNK3 in hippocampal CA1 cells (35). In our study, JNK3 activity was positively regulated by S-nitrosylation, although the target of this S-nitrosylation appears to be the JNK3 phosphatase, MKP7, and not JNK3 directly (Fig.…”

Section: Discussionmentioning

confidence: 49%

SDF-1α stimulates JNK3 activity via eNOS-dependent nitrosylation of MKP7 to enhance endothelial migration

Wu²,

Ferguson³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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The chemokine stromal cell-derived factor-1␣ (SDF-1␣) is a pivotal player in angiogenesis. It is capable of influencing such cellular processes as tubulogenesis and endothelial cell migration, yet very little is known about the actual signaling events that mediate SDF-1␣-induced endothelial cell function. In this report, we describe the identification of an intricate SDF-1␣-induced signaling cascade that involves endothelial nitric oxide synthase (eNOS), JNK3, and MAPK phosphatase 7 (MKP7). We demonstrate that the SDF-1␣-induced activation of JNK3, critical for endothelial cell migration, depends on the prior activation of eNOS. Specifically, activation of eNOS leads to production of NO and subsequent nitrosylation of MKP7, rendering the phosphatase inactive and unable to inhibit the activation of JNK3. These observations reinforce the importance of nitric oxide and S-nitrosylation in angiogenesis and provide a mechanistic pathway for SDF-1␣-induced endothelial cell migration. In addition, the discovery of this interactive network of pathways provides novel and unexpected therapeutic targets for angiogenesis-dependent diseases.

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Section: Discussionmentioning

confidence: 49%

SDF-1α stimulates JNK3 activity via eNOS-dependent nitrosylation of MKP7 to enhance endothelial migration

Wu²,

Ferguson³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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“…Previously, it was also reported that JNK signaling is activated by NO. 56 Thus, NO synthesis in glioma cells may activate JNK and sequentially cause activation of Notch signaling, thereby leading to expansion of glioma stem-like cell population. However, in endogenous neural stem cells, Notch signaling may not be regulated by JNK, because JNK signaling appears to induce apoptosis in normal neural stem cells.…”

Section: Discussionmentioning

confidence: 99%

c-Jun N-terminal kinase has a pivotal role in the maintenance of self-renewal and tumorigenicity in glioma stem-like cells

Yoon

Kim

et al. 2012

Oncogene

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Uncovering the mechanisms that govern the maintenance of stem-like cancer cells is critical for developing therapeutic strategies for targeting these cells. Constitutive activation of c-Jun N-terminal kinase (JNK) has been reported in gliomas and correlates with histological grade. Here, we found that JNK signaling is crucial for the maintenance of 'stemness' in glioma cells. Sphere-cultured glioma cells showed more phosphorylation of JNK compared with serum-containing monolayer cultures. Importantly, blockade of JNK signaling with SP600125 or small interfering RNAs targeting JNK1 or JNK2 significantly reduced the CD133 þ /Nestin þ population and suppressed sphere formation, colony formation in soft agar, and expression of stem cell markers in sphere-cultured glioma cells. Intriguingly, sphere-cultured glioma cells exhibited enhanced expression of Notch-2, but not Notch-1, -3 or -4, and JNK inhibition almost completely abrogated this increase. Blocking the phosphoinoside 3-kinase (PI3K)/Akt pathway with LY294002 or si-Akt also suppressed the self-renewal of sphere-cultured glioma cells. PI3K, but not Akt, had a role as an upstream kinase in JNK1/2 activation. In addition, treatment with si-JNK greatly increased etoposideand ionizing radiation (IR)-induced cell death in glioma spheres. Consistent with glioma cell lines, glioma stem-like cells isolated from primary patient glioma cells also had a higher activity of JNK and Notch-2 expression. Importantly, inhibition of JNK2 led to a decrease of Notch-2 expression and suppressed the CD133 þ /Nestin þ cell population in patient-derived primary glioma cells. Finally, downregulation of JNK2 almost completely suppressed intracranial tumor formation by glioma cells in nude mice. Taken together, these data demonstrate that JNK signaling is crucial for the maintenance of self-renewal and tumorigenicity of glioma stem-like cells and drug/IR resistance, and can be considered a promising target for eliminating stem-like cancer cells in gliomas.

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“…Hypoxia activated ERK, while administration of a NOS inhibitor prevented hypoxia-induced phosphorylation in neuronal nuclei of newborn piglets, suggesting that the hypoxia-induced ERK phosphorylation is NO mediated (Mishra et al 2004). In endothelial cells, hypoxia also enhanced ERK phosphorylation (Zhu et al 2003).…”

Section: Potential Indirect Effects On Nomentioning

confidence: 93%

eNOS activation and NO function: Differential control of steroidogenesis by nitric oxide and its adaptation with hypoxia

Ducsay¹,

Myers²

2011

Journal of Endocrinology

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Nitric oxide (NO) plays a role in a wide range of physiological processes. Aside from its widely studied function in the regulation of vascular function, NO has been shown to impact steroidogenesis in a number of different tissues. The goal of this review is to explore the effects of NO on steroid production and further, to discern its source(s) and mechanism of action. Attention will be given to the regulation of NO synthases in specific endocrine tissues including ovaries, testes, and adrenal glands. The effects of hypoxia on generation of NO and subsequent effects on steroid biosynthesis will also be examined. Finally, a potential model for the interaction of hypoxia on NO synthesis and steroid production is proposed.

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Nitric oxide-mediated activation of extracellular signal-regulated kinase (erk) and c-jun n-terminal kinase (jnk) during hypoxia in cerebral cortical nuclei of newborn piglets

Cited by 43 publications

References 59 publications

SDF-1α stimulates JNK3 activity via eNOS-dependent nitrosylation of MKP7 to enhance endothelial migration

SDF-1α stimulates JNK3 activity via eNOS-dependent nitrosylation of MKP7 to enhance endothelial migration

c-Jun N-terminal kinase has a pivotal role in the maintenance of self-renewal and tumorigenicity in glioma stem-like cells

eNOS activation and NO function: Differential control of steroidogenesis by nitric oxide and its adaptation with hypoxia

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