scholarly journals Propofol Inhibits Ischemia/Reperfusion-Induced Cardiotoxicity Through the Protein Kinase C/Nuclear Factor Erythroid 2-Related Factor Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Shengqiang Li ◽  
Zhen Lei ◽  
Meng Zhao ◽  
Yonghao Hou ◽  
Di Wang ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Ischemia Reperfusion ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Nuclear Factor ◽  
H9c2 Cells ◽  
Nrf2 Pathway ◽  
Kinase C ◽  
Creatine Kinase Mb

Both hydrogen peroxide (H2O2, H) and ischemia/reperfusion (I/R) can damage cardiomyocytes, which was inhibited by propofol (P). The present research was designed to examine whether propofol can reduce myocardial I/R injury by activating protein kinase C (PKC)/nuclear factor erythroid-2-related factor 2 (NRF2) pathway in H9C2 cells and rat Langendorff models. H9C2 cells were disposed of no reagents (C), H2O2 for 24 h (H), propofol for 1 h before H2O2 (H+P), and chelerythrine (CHE, PKC inhibitor) for 1 h before propofol and H2O2 (H+P+CHE). N = 3. The PKC gene of H9C2 was knocked down by siRNA and overexpressed by phorbol 12-myristate 13-acetate (PMA, PKC agonist). The cell viability and the expressions of PKC, NRF2, or heme oxygenase-1(HO-1) were evaluated. Propofol significantly reduced H9C2 cell mortality induced by H2O2, and significantly increased NRF2 nuclear location and HO-1 expression, which were restrained by siRNA knockout of PKC and promoted by PMA. Rat hearts were treated with KrebsHenseleit solution for 120 min (C), with (I/R+P) or without (I/R) propofol for 20 min before stopping perfusion for 30 min and reperfusion for 60 min, and CHE for 10 min before treated with propofol. N = 6. The levels of lactate dehydrogenase (LDH), superoxide dismutase (SOD), and creatine kinase-MB (CK-MB) in perfusion fluid and antioxidant enzymes in the myocardium were assessed. I/R, which increased LDH and CK-MB expression and reduced SOD expression, boosted the pathological damage and infarcts of the myocardium after reperfusion. However, propofol restrained all these effects, an activity that was antagonized by CHE. The results suggest that propofol pretreatment protects against I/R injury by activating of PKC/NRF2 pathway.

scholarly journals The Skin-Whitening Effects of Ectoine via the Suppression of α-MSH-Stimulated Melanogenesis and the Activation of Antioxidant Nrf2 Pathways in UVA-Irradiated Keratinocytes

Antioxidants ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 63 ◽  
Author(s):  
You-Cheng Hseu ◽  
Xuan-Zao Chen ◽  
Yugandhar Vudhya Gowrisankar ◽  
Hung-Rong Yen ◽  
Jing-Yuan Chuang ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Molecular Mechanisms ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Hacat Cells ◽  
Skin Whitening ◽  
B16f10 Cells ◽  
Kinase C ◽  
Protein Kinase Ckii

Ultraviolet A (UVA)-irradiation induced reactive oxygen species (ROS) production mediates excessive melanogenesis in skin cells leading to pigmentation. We demonstrated the depigmenting and anti-melanogenic effects of Ectoine, a natural bacterial osmolyte, in UVA-irradiated human (HaCaT) keratinocytes, and the underlying molecular mechanisms were elucidated. HaCaT cells were pre-treated with low concentrations of Ectoine (0.5–1.5 μM) and assayed for various depigmenting and anti-melanogenic parameters. This pre-treatment significantly downregulated ROS generation, α-melanocyte-stimulating hormone (α-MSH) production, and proopiomelanocortin (POMC) expression in UVA-irradiated HaCaT cells. Also, antioxidant heme oxygenase-1 (HO-1), NAD(P)H dehydrogenase [quinone 1] (NQO-1), and γ-glutamate-cysteine ligase catalytic subunit (γ-GCLC) protein expressions were mediated via the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) whose knockdown indeed impaired this effect signifying the importance of the Nrf2 pathway. Ectoine was mediating the activation of Nrf2 via the p38, protein kinase B (also known as AKT), protein kinase C (PKC), and casein kinase II protein kinase (CKII) pathways. The conditioned medium obtained from the Ectoine pre-treated and UVA-irradiated HaCaT cells downregulated the tyrosinase, tyrosinase-related protein-1 and -2 (TRP-1/-2), cyclic AMP (c-AMP) protein kinase, c-AMP response element-binding protein (CREB), and microphthalmia-associated transcription factor (MITF) expressions leading to melanoma B16F10 cells having inhibited melanin synthesis. Interestingly, this anti-melanogenic effect in α-MSH-stimulated B16F10 cells was observable only at 50–400 μM concentrations of Ectoine, signifying the key role played by Ectoine (0.5–1 μM)-treated keratinocytes in skin whitening effects. We concluded that Ectoine could be used as an effective topical natural cosmetic agent with depigmenting and anti-melanogenic efficacy.

Atypical protein kinase C mediates activation of NF-E2-related factor 2 in response to oxidative stress

2003 ◽  
Vol 285 (2) ◽  
pp. C334-C342 ◽  
Author(s):  
Satoshi Numazawa ◽  
Makie Ishikawa ◽  
Aya Yoshida ◽  
Sachiko Tanaka ◽  
Takemi Yoshida
Keyword(s):  
Oxidative Stress ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Prolonged Exposure ◽  
Fluorescent Protein ◽  
Nuclear Translocation ◽  
Kinase Assay ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Kinase C

Transcription factor NF-E2-related factor 2 (Nrf2) regulates the induction of antioxidative proteins, including heme oxygenase-1 (HO-1). Nrf2 is sequestered in the cytoplasm by Keap1 under unstimulated conditions but translocates into the nucleus and transactivates the antioxidant responsive element (ARE) upon exposure to oxidative insults. It has recently been demonstrated that in vitro phosphorylation of Nrf2 on Ser40 by protein kinase C (PKC) facilitates the dissociation of Nrf2 from the Keap1 complex (Huang HC, Nguyen T, and Pickett CB. J Biol Chem 277: 42769–42774, 2002). The present study was designed to examine whether PKC is involved in oxidative stress-mediated nuclear translocation of Nrf2 in vivo and, if so, which PKC isoforms are involved. Induction of HO-1 gene expression by phorone, a glutathione depletor, and 4-hydroxy-2,3-nonenal (4-HNE), an end product of lipid peroxidation, was suppressed by a specific PKC inhibitor, Ro-31-8220, at concentrations that inhibit all isoforms in WI-38 cells. The induction of HO-1 was not affected by prolonged exposure of the cells to 12- O-tetradecanoylphorbol-13 acetate (TPA), suggesting that TPA-insensitive atypical PKC (aPKC) isoforms are involved. An immunocomplex kinase assay revealed that phorone and 4-HNE increased aPKCι activity. In COS-7 cells, 4-HNE induced nuclear translocation of the Nrf2-green fluorescent protein (GFP) fusion protein, but not the Nrf2(S40A)-GFP mutant. In the absence of oxidative insults, the Nrf2(S40E)-GFP mutant was distributed in the nucleus. The Nrf2-GFP accumulation in the nucleus was induced by coexpression of aPKCι, but not by a kinase inactive mutant aPKCι(K274W). The activity of an ARE-driven reporter was increased by coexpression of aPKCι, and this effect was eliminated by Ro-31-8220 in HepG2 cells. The reporter activity induced by 4-HNE was inhibited by coexpression of aPKCι(K274W). These results suggest that phosphorylation of Nrf2 Ser40 by aPKC(s) is involved in the nuclear translocation and ARE transactivation of Nrf2 by oxidative stress.

Trilobatin Protects Cardiomyocytes from Hypoxia/ Reperfusion Injury by Regulating the Nuclear Factor Erythroid 2-Related Factor 2/Heme Oxygenase-1 Pathway

2020 ◽  
Vol 19 (2) ◽  
pp. 133-138
Author(s):  
Wenyu Chen ◽  
Hui He
Keyword(s):  
Heme Oxygenase ◽  
Molecular Mechanisms ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Cellular Injury ◽  
Nuclear Factor ◽  
Oxygen Species ◽  
H9c2 Cells ◽  
Natural Plant ◽  
Induced Changes

Trilobatin is a natural plant-derived glycosylated flavonoid that has been shown to exhibit multiple beneficial pharmacologic activities including protection of heart against H/R-induced cardiomyocyte injury. However, the molecular mechanisms underlying protection from H/R-induced cardiomyocyte injury remain unknown. Using H9C2 cells as a model, we examined the effect of trilobatin on H/R-induced cellular injury, apoptosis, and generation of reactive oxygen species. The results showed that trilobatin protected H9C2 cells not only from cell death and apoptosis, but also counteracted H/R-induced changes in malondialdehyde, superoxide dismutase, glutathione, and glutathione peroxidase. The evaluation of the mechanism underlying the effect of trilobatin on protection from H/R-induced cellular injury suggested changes in the regulation of nuclear factor erythroid 2-related factor 2/heme oxygenase-1 pathway.

scholarly journals Activation of Nuclear Factor κB (NF-κB) in Prostate Cancer Is Mediated by Protein Kinase C ϵ (PKCϵ)

2012 ◽  
Vol 287 (44) ◽  
pp. 37570-37582 ◽  
Author(s):  
Rachana Garg ◽  
Jorge Blando ◽  
Carlos J. Perez ◽  
HongBin Wang ◽  
Fernando J. Benavides ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Kinase C

Mechanism of Hepatic Heme Oxygenase-1 Induction by Isoflurane

2006 ◽  
Vol 104 (1) ◽  
pp. 101-109 ◽  
Author(s):  
Alexander Hoetzel ◽  
Daniel Leitz ◽  
Rene Schmidt ◽  
Eva Tritschler ◽  
Inge Bauer ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Phospholipase A2 ◽  
Heme Oxygenase ◽  
Kupffer Cell ◽  
Cell Function ◽  
Heme Oxygenase 1 ◽  
Gadolinium Chloride ◽  
Kinase C

Background The heme oxygenase pathway represents a major cell and organ protective system in the liver. The authors recently showed that isoflurane and sevoflurane up-regulate the inducible isoform heme oxygenase 1 (HO-1). Because the activating cascade remained unclear, it was the aim of this study to identify the underlying mechanism of this effect. Methods Rats were anesthetized with pentobarbital intravenously or with isoflurane per inhalation (2.3 vol%). Kupffer cell function was inhibited by dexamethasone or gadolinium chloride. Nitric oxide synthases were inhibited by either N(omega)-nitro-L-arginine methyl ester or S-methyl thiourea. N-acetyl-cysteine served as an antioxidant, and diethyldithiocarbamate served as an inhibitor of cytochrome P450 2E1. Protein kinase C and phospholipase A2 were inhibited by chelerythrine or quinacrine, respectively. HO-1 was analyzed in liver tissue by Northern blot, Western blot, immunostaining, and enzymatic activity assay. Results In contrast to pentobarbital, isoflurane induced HO-1 after 4-6 h in hepatocytes in the pericentral region of the liver. The induction was prevented in the presence of dexamethasone (P < 0.05) and gadolinium chloride (P < 0.05). Inhibition of nitric oxide synthases or reactive oxygen intermediates did not affect isoflurane-mediated HO-1 up-regulation. In contrast, chelerythrine (P < 0.05) and quinacrine (P < 0.05) resulted in a blockade of HO-1 induction. Conclusion The up-regulation of HO-1 by isoflurane in the liver is restricted to parenchymal cells and depends on Kupffer cell function. The induction is independent of nitric oxide or reactive oxygen species but does involve protein kinase C and phospholipase A2.

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