scholarly journals IGF-I inhibition of apoptosis is associated with decreased expression of prostate apoptosis response-4

2007 ◽  
Vol 194 (1) ◽  
pp. 77-85 ◽  
Author(s):  
Hyunju Chung ◽  
Sanghee Seo ◽  
Minho Moon ◽  
Seungjoon Park
Keyword(s):  
Protein Kinase ◽  
Pc12 Cells ◽  
Nuclear Translocation ◽  
Neuronal Damage ◽  
Apoptotic Cell ◽  
Glucose Deprivation ◽  
Inhibitory Effect ◽  
Igf I ◽  
Apoptotic Effect ◽  
Protein Kinase C Inhibitor

The neuronal damage caused by ischemic brain injury is associated with increased apoptosis. IGF-I exposure promotes neuronal defense and survival against ischemic insult by inhibiting apoptotic processes. We investigated the role of prostate apoptosis response-4 (Par-4), a proapoptotic gene the expression of which is increased after ischemic injury, in IGF-I-mediated inhibition of apoptosis using PC12 cells exposed to oxygen–glucose deprivation (OGD). The OGD insult resulted in significant increases in apoptotic cell death and Par-4 expression, which were prevented by the treatment of cells with an antisense oligonucleotide of Par-4. IGF-I treatment prior to OGD insult significantly reduced the number of apoptotic cells and the OGD-induced increase in Par-4 expression. OGD-induced nuclear translocation of Par-4 was also attenuated by IGF-I treatment. In addition, we demonstrated that the anti-apoptotic effect of IGF-I was blocked by chemical inhibition of a mitogen activated protien kinase (MAPK), phosphatidylinositol 3-kinase (PI3K), or protein kinase A (PKA), but not by a protein kinase C inhibitor. Finally, pretreatment of cells with a MAPK or PI3K inhibitor attenuated IGF-I-induced inhibition of Par-4 expression, suggesting that the MAPK and PI3K pathways contribute to IGF-I-induced Par-4 suppression. In contrast, a PKA inhibitor failed to alter the inhibitory effect of IGF-I on Par-4. These findings indicate that in PC12 cells exposed to OGD insult, IGF-I protects cells from apoptosis, at least in part through the inhibition of Par-4 expression.

scholarly journals Curcumin Efficacy in a Serum/glucose Deprivation-induced Neuronal PC12 Injury Model

2021 ◽  
Vol 14 ◽  
Author(s):  
Tahereh Farkhondeh ◽  
Milad Ashrafizadeh ◽  
Mohsen Azimi-Nezhad ◽  
Fariborz Samini ◽  
Micheal Aschenr ◽  
...  
Keyword(s):  
Cell Viability ◽  
Pc12 Cells ◽  
Molecular Mechanisms ◽  
Neuronal Damage ◽  
Glucose Deprivation ◽  
Serum Glucose ◽  
Protective Effects ◽  
Injury Model ◽  
Apoptotic Effect ◽  
Underlying Mechanisms

Background: Glucose/serum deprivation (GSD), has been used for understanding molecular mechanisms of neuronal damage during ischemia. It has been suggested that curcumin may improve neurodegenerative diseases. Aim: In this study, the protective effects of curcumin and its underlying mechanisms were investigated in PC12 cells upon GSD-induced stress. Methods: PC12 cells were cultured in DMEM overnight and then incubated in GSD condition for either 6 or 12h. GSD-treated cells were pretreated with various concentrations of curcumin (10, 20, and 40 M) for 5h. The cell viability, apoptosis, reactive oxygen species (ROS) level, oxidative stress, expression of apoptosis-related genes, and IL-6 were determined. Results: Curcumin increased cell viability and caused an anti-apoptotic effect in PC12 cells exposed for 12h to GSD . Curcumin also increased antioxidant enzyme expression, suppressed lipid peroxidation, and decreased interleukin-6 secretion in PC12 cells subjected to GSD. In addition, pretreatment with curcumin down-regulated pro-apoptotic (Bax), and up-regulated antiapoptotic (Bcl2) mediators. Conclusion: Curcumin mitigates many of the adverse effects of ischemia, and therefore, should be considered as an adjunct therapy in ischemic patients.

Caerulein-induced NF-κB/Rel activation requires both Ca2+ and protein kinase C as messengers

1999 ◽  
Vol 277 (3) ◽  
pp. G678-G686 ◽  
Author(s):  
Yusuke Tando ◽  
Hana Algül ◽  
Martin Wagner ◽  
Hans Weidenbach ◽  
Guido Adler ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Nuclear Translocation ◽  
Inhibitory Effect ◽  
Binding Activity ◽  
Atpase Inhibitor ◽  
Kinase C ◽  
Protein Kinase C Activity ◽  
Intracellular Ca ◽  
Iκbα Degradation

The eukaryotic transcription factor NF-κB/Rel is activated by a large variety of stimuli. We have recently shown that NF-κB/Rel is induced during the course of caerulein pancreatitis. Here, we show that activation of NF-κB/Rel by caerulein, a CCK analog, requires increasing intracellular Ca2+ levels and protein kinase C activation. Caerulein induces a dose-dependent increase of nuclear NF-κB/Rel binding activity in pancreatic lobules, which is paralleled by degradation of IκBα. IκBβ was only slightly affected by caerulein treatment. Consistent with an involvement of Ca2+, the endoplasmic reticulum-resident Ca2+-ATPase inhibitor thapsigargin activated NF-κB/Rel in pancreatic lobules. The intracellular Ca2+ chelator TMB-8 prevented IκBα degradation and subsequent nuclear translocation of NF-κB/Rel induced by caerulein. BAPTA-AM was less effective. Cyclosporin A, a Ca2+/calmodulin-dependent protein phosphatase (PP2B) inhibitor, decreased caerulein-induced NF-κB/Rel activation and IκBα degradation. The inhibitory effect of bisindolylmaleimide suggests that protein kinase C activity is also required for caerulein-induced NF-κB/Rel activation. These data suggest that Ca2+- as well as protein kinase C-dependent mechanisms are required for caerulein-induced NF-κB/Rel activation.

scholarly journals Comparative Study of White and Black Sesame by Using Oxygen Glucose Deprivation on PC12 Cells

2019 ◽  
Vol 5 (1) ◽  
pp. 9-13
Author(s):  
Nirmala Jamarkattel-Pandit
Keyword(s):  
Comparative Study ◽  
Pc12 Cells ◽  
Crude Extract ◽  
Neuronal Damage ◽  
Ischemia Reperfusion ◽  
Glucose Deprivation ◽  
Sesamum Indicum ◽  
Biological Study ◽  
Oxygen Glucose Deprivation ◽  
Baked Goods

Sesame (Sesamum indicum L.) is one of the most important oilseed crops in the world. It is not only a source of edible oil, but also widely used in baked goods and confectionery products. Sesame seed varies considerably in color, size, and texture of the seed coat. The most commonly used are of white and black sesame, having almost same pharmacological activity and contain almost same components. However, it is reported that the components, such as Se, Zn, Fe, Mg, sesamin, and vitamin E, are different between the white and the black coat sesame. Active components of sesame seeds has been reported as protective effects against neuronal damage induced by chemical hypoxia or hydrogen peroxide but there was no sufficient biological study of white sesame and black sesame. In present study, oxygen and glucose deprivation followed by reoxygenation (OGD-R) model, an in vitro model of cerebral ischemia/reperfusion was used to investigate the effects and comparative study of white sesame and black sesame on different cell lines. This result clearly demonstrated that crude extract of white sesame is superior than crude extract of black sesame and fractions of white sesame and black sesame protected PC12 cells from hypoxia-induced stress. Keywords: Oxygen glucose deprivation, PC12 Cells, Ischemia model, Sesamum indicum L.

Localization of IP in rabbit kidney and functional role of the PGI2/IP system in cortical collecting duct

2002 ◽  
Vol 283 (4) ◽  
pp. F689-F698 ◽  
Author(s):  
Rania Nasrallah ◽  
Rolf M. Nusing ◽  
Richard L. Hébert
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Functional Role ◽  
Collecting Duct ◽  
Inhibitory Effect ◽  
Rabbit Kidney ◽  
Cortical Collecting Duct ◽  
Kinase C ◽  
Protein Kinase C Inhibitor

To clarify the role of the PGI2/PGI2 receptor (IP) system in rabbit cortical collecting duct (RCCD), we characterized the expression of IP receptors in the rabbit kidney. We show by Northern and Western blotting that IP mRNA and protein was detectable in all three regions of the kidney. To determine how PGI2 signals, we compared the effects of different PGI2 analogs [iloprost (ILP), carba-prostacyclin (c-PGI2), and cicaprost (CCP)] in the isolated perfused RCCD. PGI2 analogs did not increase water flow ( L p). Although PGI2 analogs did not reduce an established L p response to 8-chlorophenylthio-cAMP, they equipotently inhibited AVP-stimulated L p by 45%. The inhibitory effect of ILP and c-PGI2 on AVP-stimulated L p is partially reversed by the protein kinase C inhibitor staurosporine and abolished by pertussis toxin; no effect was obtained with CCP. In fura 2-loaded RCCD, CCP did not alter cytosolic Ca2+concentration ([Ca2+]i), but, in the presence of CCP, individual infusion of ILP and PGE2 increased [Ca2+]i, suggesting that CCP did not cause desensitization to either ILP or PGE2. We concluded that ILP and c-PGI2 activate PKC and the liberation of [Ca2+]i but not CCP. This suggested an important role for phosphatidylinositol hydrolysis in mediating ILP and c-PGI2 effects but not CCP in RCCD.

Anti-apoptotic Effect of Taxodione on Serum/Glucose Deprivation-Induced PC12 Cells Death

2014 ◽  
Vol 34 (8) ◽  
pp. 1103-1109 ◽  
Author(s):  
Negar Shafaei-Bajestani ◽  
Seyed Ahmad Emami ◽  
Javad Asili ◽  
Zahra Tayarani-Najaran
Keyword(s):  
Pc12 Cells ◽  
Glucose Deprivation ◽  
Serum Glucose ◽  
Apoptotic Effect ◽  
Cells Death

scholarly journals ERK1/2-p90RSK-mediated Phosphorylation of Na+/H+ Exchanger Isoform 1

2007 ◽  
Vol 282 (38) ◽  
pp. 28274-28284 ◽  
Author(s):  
Jing Luo ◽  
Douglas B. Kintner ◽  
Gary E. Shull ◽  
Dandan Sun
Keyword(s):  
Nuclear Translocation ◽  
Neuronal Damage ◽  
Glucose Deprivation ◽  
Mek Inhibitor ◽  
Oxygen And Glucose Deprivation ◽  
Genetic Ablation ◽  
Extracellular Signal ◽  
Nhe1 Activity ◽  
Ribosomal S6 Kinase

The function and regulation of Na+/H+ exchanger isoform 1 (NHE1) following cerebral ischemia are not well understood. In this study, we demonstrate that extracellular signal-related kinases (ERK1/2) play a role in stimulation of neuronal NHE1 following in vitro ischemia. NHE1 activity was significantly increased during 10-60 min reoxygenation (REOX) after 2-h oxygen and glucose deprivation (OGD). OGD/REOX not only increased the Vmax for NHE1 but also shifted the Km toward decreased [H+]i. These changes in NHE1 kinetics were absent when MAPK/ERK kinase (MEK) was inhibited by the MEK inhibitor U0126. There were no changes in the levels of phosphorylated ERK1/2 (p-ERK1/2) after 2 h OGD. The p-ERK1/2 level was significantly increased during 10-60 min REOX, which was accompanied by nuclear translocation. U0126 abolished REOX-induced elevation and translocation of p-ERK1/2. We further examined the ERK/90-kDa ribosomal S6 kinase (p90RSK) signaling pathways. At 10 min REOX, phosphorylated NHE1 was increased with a concurrent elevation of phosphorylation of p90RSK, a known NHE1 kinase. Inhibition of MEK activity with U0126 abolished phosphorylation of both NHE1 and p90RSK. Moreover, neuroprotection was observed with U0126 or genetic ablation or pharmacological inhibition of NHE1 following OGD/REOX. Taken together, these results suggest that activation of ERK1/2-p90RSK pathways following in vitro ischemia phosphorylates NHE1 and increases its activity, which subsequently contributes to neuronal damage.

scholarly journals Selective nuclear translocation of protein kinase C α in Swiss 3T3 cells treated with IGF-I, PDGF and EGF

FEBS Letters ◽  
1994 ◽  
Vol 347 (1) ◽  
pp. 63-68 ◽  
Author(s):  
Luca M. Neri ◽  
Anna Maria Billi ◽  
Lucia Manzoli ◽  
Silvia Rubbini ◽  
R.Stewart Gilmour ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Nuclear Translocation ◽  
3T3 Cells ◽  
Kinase C ◽  
Igf I ◽  
Swiss 3T3

Permissive effect of EGFR-activated pathways on RVI and their anti-apoptotic effect in hypertonicity-exposed mIMCD3 cells

2011 ◽  
Vol 31 (6) ◽  
pp. 489-497 ◽  
Author(s):  
Alejandro Ruiz-Martínez ◽  
Erika Vázquez-Juárez ◽  
Gerardo Ramos-Mandujano ◽  
Herminia Pasantes-Morales
Keyword(s):  
Cell Death ◽  
Protein Kinase ◽  
Apoptotic Cell ◽  
Growth Factor Receptor ◽  
Mitogen Activated Protein Kinase ◽  
Egfr Inhibition ◽  
Mitogen Activated Protein ◽  
Apoptotic Effect ◽  
Phosphoinositide 3 Kinase

Hypertonicity is a stressful stimulus leading to cell shrinkage and apoptotic cell death. Apoptosis can be prevented if cells are able to activate the mechanism of RVI (regulatory volume increase). This study in mIMCD3 cells presents evidence of a permissive role of the EGFR (epidermal growth factor receptor) on RVI, achieved for the most part through the two main EGFR-triggered signalling chains, the MAPK (mitogen-activated protein kinase)/ERK (extracellular-signal-regulated kinase) and the PI3K (phosphoinositide 3-kinase)/Akt (also known as protein kinase B) pathways. Hyperosmotic solutions (450 mosM) made by addition of NaCl, increased EGFR phosphorylation, which is prevented by GM6001 and AG1478, blockers respectively, of MMPs (matrix metalloproteinases) and EGFR. Inhibition of EGFR, ERK (PD98059) or PI3K/Akt (wortmannin) phosphorylation reduced RVI by 60, 48 and 58% respectively. The NHE (Na+/H+ exchanger) seems to be the essential mediator of this effect since (i) NHE is the main contributor to RVI, (ii) EGFR, ERK and PI3K/Akt blockers added together with the NHE blocker zoniporide reduce RVI by non-additive effects and (iii) All the blockers significantly lowered the NHE rate in cells challenged by an NH4Cl pulse. Besides reducing RVI, the inhibition of MMP, EGFR and PI3K/Akt had a strong pro-apoptotic effect increasing cell death by 2–3.7-fold. This effect was significantly lower when RVI inhibition did not involve the EGFR-PI3K/Akt pathway. These results provide evidence that Akt and its permissive effect on RVI have a predominant influence on cell survival under hypertonic conditions in IMCD3 cells. This role of Akt operates under the influence of EGFR activation, promoted by MMP.

scholarly journals Protective Effect ofPunica granatumL. against Serum/Glucose Deprivation-Induced PC12 Cells Injury

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Fatemeh Forouzanfar ◽  
Amir Afkhami Goli ◽  
Elham Asadpour ◽  
Ahmad Ghorbani ◽  
Hamid Reza Sadeghnia
Keyword(s):  
Dna Damage ◽  
Cell Viability ◽  
Pc12 Cells ◽  
Molecular Mechanisms ◽  
Neuronal Damage ◽  
Glucose Deprivation ◽  
Serum Glucose ◽  
Pomegranate Juice ◽  
Significant Difference ◽  
Anti Inflammatory

The discovery and development of natural products with potent antioxidant, anti-inflammatory, and antiapoptotic properties have been one of the most interesting and promising approaches in the search for the treatment of many neurodegenerative diseases including ischemic stroke. Serum/glucose deprivation (SGD) has served as an excellent in vitro model for the understanding of the molecular mechanisms of neuronal damage during ischemia and for the development of neuroprotective drugs against ischemia-induced brain injury. Recent studies suggested that pomegranate (Punica granatumL.) or its active constituents exert pharmacological actions such as antioxidant, anti-inflammatory, and neuroprotective properties. Therefore, in this study we investigated the possible protective effects of different extracts of pomegranate against SGD-induced PC12 cells injury. Initially, the cells were pretreated with different concentrations of pulp hydroalcoholic extract (PHE), pulp aqueous extract (PAE) and pomegranate juice (PJ) for 2 h and then deprived of serum/glucose (SGD) for 6 and 12 h. SGD caused a significant reduction in cell viability (measured by the MTT assay) after 6 and 12 h, as compared with control cells (P<0.001). Pretreatment with PHE, PAE, and PJ significantly and concentration-dependently increased cell viability following SGD insult for 6 and 12 h. A significant increase in DNA damage (measured by the comet assay) was seen in nuclei of cells following SGD for 12 h (P<0.001). In control groups, no significant difference was seen in DNA damage between PHE, PAE, and PJ-pretreated and vehicle-pretreated PC12 cells (P>0.05). PHE, PAE, and PJ pretreatment resulted in a significant decrease in DNA damage following ischemic insult (P<0.001). This suppression of DNA damage by PHE, PAE and PJ was found to be concentration dependent. These data indicate that there is a cytoprotective property in PHE, PAE, and PJ under SGD condition in PC12 cells, suggesting that pomegranate has the potential to be used as a new therapeutic strategy for neurodegenerative disorders.

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