Neuroglobin Promotes Neurite Outgrowth via Differential Binding to PTEN and Akt

Li, Li; Liu, Qian Rong; Xiong, Xin; Liu, Ju Mei; Lai, Xiao Jing; Cheng, Chun; Pan, Feng; Chen, Yong; Shang, Yu; Yu, Albert Cheung Hoi; Chen, Xiao Qian

doi:10.1007/s12035-013-8506-7

Cited by 34 publications

(42 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Western blot analysis was performed as described previously [26, 27]. Briefly, cells were seeded in 35 mm dishes and incubated for 24 h. After PL treatment for 6 h, cells were scratched and incubated in DMEM supplemented with 20% FBS for another 3 h. For the whole cell lysates, the cells were gathered in RIPA lysis buffer (Beyotime, Nantong, China) and sonicated.…”

Section: Methodsmentioning

confidence: 99%

Piperlongumine Inhibits Migration of Glioblastoma Cells via Activation of ROS-Dependent p38 and JNK Signaling Pathways

Liu

Chen

et al. 2014

Oxidative Medicine and Cellular Longevity

Self Cite

View full text Add to dashboard Cite

Piperlongumine (PL) is recently found to kill cancer cells selectively and effectively via targeting reactive oxygen species (ROS) responses. To further explore the therapeutic effects of PL in cancers, we investigated the role and mechanisms of PL in cancer cell migration. PL effectively inhibited the migration of human glioma (LN229 or U87 MG) cells but not normal astrocytes in the scratch-wound culture model. PL did not alter EdU+-cells and cdc2, cdc25c, or cyclin D1 expression in our model. PL increased ROS (measured by DCFH-DA), reduced glutathione, activated p38 and JNK, increased IκBα, and suppressed NFκB in LN229 cells after scratching. All the biological effects of PL in scratched LN229 cells were completely abolished by the antioxidant N-acetyl-L-cysteine (NAC). Pharmacological administration of specific p38 (SB203580) or JNK (SP600125) inhibitors significantly reduced the inhibitory effects of PL on LN229 cell migration and NFκB activity in scratch-wound and/or transwell models. PL prevented the deformation of migrated LN229 cells while NAC, SB203580, or SP600125 reversed PL-induced morphological changes of migrated cells. These results suggest potential therapeutic effects of PL in the treatment and prevention of highly malignant tumors such as glioblastoma multiforme (GBM) in the brain by suppressing tumor invasion and metastasis.

show abstract

Section: Methodsmentioning

confidence: 99%

Piperlongumine Inhibits Migration of Glioblastoma Cells via Activation of ROS-Dependent p38 and JNK Signaling Pathways

Liu

Chen

et al. 2014

Oxidative Medicine and Cellular Longevity

Self Cite

View full text Add to dashboard Cite

show abstract

“…42 Freshly isolated neurons (5 × 10 6 /35-mm dish) were transfected with plasmids by using the Nucleofector Kit and the Amaxa Nucleofector device (Lonza, Basel, Switzerland) according to the manufacturer's instructions. 42 Cultures were maintained in neurobasal media supplemented with 2% B27 and 2 mM L-glutamine (Invitrogen, Grand Island, NY, USA) 24 h after initial seeding, and half of the media was replenished every 2 days in vitro (DIV). The cultures were used for experiments at 7 DIV.…”

Section: Methodsmentioning

confidence: 99%

“…Equal amounts of total proteins were subjected to western blotting analysis as previously described. 42 The membranes were blocked with 5% (w/v) nonfat dried milk in Tris-buffered saline and then incubated with primary antibodies. After incubation with IRDye 800CW or IRDye 680CW conjugated goat anti-rabbit or anti-mouse IgG (Licor Biosciences, Lincoln, NE, USA), the blots were visualized and quantified by using the Odyssey Infrared Imaging System (Licor Biosciences).…”

Section: Methodsmentioning

confidence: 99%

Selective 14-3-3γ induction quenches p-β-catenin Ser37/Bax-enhanced cell death in cerebral cortical neurons during ischemia

Lai

Zheng

et al. 2014

Cell Death Dis

View full text Add to dashboard Cite

Ischemia-induced cell death is a major cause of disability or death after stroke. Identifying the key intrinsic protective mechanisms induced by ischemia is critical for the development of effective stroke treatment. Here, we reported that 14-3-3γ was a selective ischemia-inducible survival factor in cerebral cortical neurons reducing cell death by downregulating Bax depend direct 14-3-3γ/p-β-catenin Ser37 interactions in the nucleus. 14-3-3γ, but not other 14-3-3 isoforms, was upregulated in primary cerebral cortical neurons upon oxygen–glucose deprivation (OGD) as measured by quantitative PCR, western blot and fluorescent immunostaining. The selective induction of 14-3-3γ in cortical neurons by OGD was verified by the in vivo ischemic stroke model. Knocking down 14-3-3γ alone or inhibiting 14-3-3/client interactions was sufficient to induce cell death in normal cultured neurons and exacerbate OGD-induced neuronal death. Ectopic overexpression of 14-3-3γ significantly reduced OGD-induced cell death in cultured neurons. Co-immunoprecipitation and fluorescence resonance energy transfer demonstrated that endogenous 14-3-3γ bound directly to more p-β-catenin Ser37 but not p-Bad, p-Ask-1, p-p53 and Bax. During OGD, p-β-catenin Ser37 but not p-β-catenin Ser45 was increased prominently, which correlated with Bax elevation in cortical neurons. OGD promoted the entry of 14-3-3γ into the nuclei, in correlation with the increase of nuclear p-β-catenin Ser37 in neurons. Overexpression of 14-3-3γ significantly reduced Bax expression, whereas knockdown of 14-3-3γ increased Bax in cortical neurons. Abolishing β-catenin phosphorylation at Ser37 (S37A) significantly reduced Bax and cell death in neurons upon OGD. Finally, 14-3-3γ overexpression completely suppressed β-catenin-enhanced Bax and cell death in neurons upon OGD. Based on these data, we propose that the 14-3-3γ/p-β-catenin Ser37/Bax axis determines cell survival or death of neurons during ischemia, providing novel therapeutic targets for ischemic stroke as well as other related neurological diseases.

show abstract

“…The Western blotting analyses were performed as previously described [18] . The total soluble proteins were extracted from the primary BMMNCs using radio-immunoprecipitation assay (RIPA) lysis buffer (Applygen Technologies Incorporation, …”

Section: Western Blotting Analysesmentioning

confidence: 99%

Piperlongumine induces apoptotic and autophagic death of the primary myeloid leukemia cells from patients via activation of ROS-p38/JNK pathways

Xiong¹,

Liu²,

Qiu

et al. 2015

Acta Pharmacol Sin

Self Cite

View full text Add to dashboard Cite

Aim: To investigate the effects of piperlongumine (PL), an anticancer alkaloid from long pepper plants, on the primary myeloid leukemia cells from patients and the mechanisms of action. Methods: Human BM samples were obtained from 9 patients with acute or chronic myeloid leukemias and 2 patients with myelodysplastic syndrome (MDS). Bone marrow mononuclear cells (BMMNCs) were isolated and cultured. Cell viability was determined using MTT assay, and apoptosis was examined with PI staining or flow cytometry. ROS levels in the cells were determined using DCFH-DA staining and flow cytometry. Expression of apoptotic and autophagic signaling proteins was analyzed using Western blotting. Results: PL inhibited the viability of BMMNCs from the patients with myeloid leukemias (with IC 50 less than 20 μmol/L), but not that of BMMNCs from a patient with MDS. Furthermore, PL (10 and 20 μmol/L) induced apoptosis of BMMNCs from the patients with myeloid leukemias in a dose-dependent manner. PL markedly increased ROS levels in BMMNCs from the patients with myeloid leukemias, whereas pretreatment with the antioxidant N-acetyl-L-cysteine abolished PL-induced ROS accumulation and effectively reduced PL-induced cytotoxicity. Moreover, PL markedly increased the expression of the apoptotic proteins (Bax, Bcl-2, and caspase-3) and autophagic proteins (Beclin-1 and LC3B), and phosphorylation of p38 and JNK in BMMNCs from the patients with myeloid leukemias, whereas pretreatment with the specific p38 inhibitor SB203580 or the specific JNK inhibitor SP600125 partially reversed PL-induced ROS production, apoptotic/autophagic signaling activation and cytotoxicity. Conclusion: Piperlongumine induces apoptotic and autophagic death of the primary myeloid leukemia cells from patients via activation of ROS-p38/JNK pathways.

show abstract

Neuroglobin Promotes Neurite Outgrowth via Differential Binding to PTEN and Akt

Cited by 34 publications

References 32 publications

Piperlongumine Inhibits Migration of Glioblastoma Cells via Activation of ROS-Dependent p38 and JNK Signaling Pathways

Piperlongumine Inhibits Migration of Glioblastoma Cells via Activation of ROS-Dependent p38 and JNK Signaling Pathways

Selective 14-3-3γ induction quenches p-β-catenin Ser37/Bax-enhanced cell death in cerebral cortical neurons during ischemia

Piperlongumine induces apoptotic and autophagic death of the primary myeloid leukemia cells from patients via activation of ROS-p38/JNK pathways

Contact Info

Product

Resources

About