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Cell signaling through protein kinase C oxidation and activation.

Cosentino-Gomes D, Rocco-Machado N, Meyer-Fernandes JR - Int J Mol Sci (2012)

Bottom Line: In this context, protein kinases and phosphatases, which act coordinately in the regulation of signal transduction through the phosphorylation and dephosphorylation of target proteins, have been described to be key elements in ROS-mediated signaling events.The major mechanism by which these proteins may be modified by oxidation involves the presence of key redox-sensitive cysteine residues.These proteins have been shown to contain a unique structural feature that is susceptible to oxidative modification.

View Article: PubMed Central - PubMed

Affiliation: Institute of Medical Biochemistry, Federal University of Rio de Janeiro (UFRJ), CCS, Bloco H, Cidade Universitária, Ilha do Fundão, 21941-590, Rio de Janeiro, RJ, Brazil; E-Mails: rocco@bioqmed.ufrj.br (N.R.-M.); meyer@bioqmed.ufrj.br (J.R.M.-F.) ; Institute of National Science and Technology of Structural Biology and Bioimage (INCTBEB), CCS, Bloco H, Cidade Universitária, Ilha do Fundão, 21941-590, Rio de Janeiro, RJ, Brazil.

ABSTRACT
Due to the growing importance of cellular signaling mediated by reactive oxygen species (ROS), proteins that are reversibly modulated by these reactant molecules are of high interest. In this context, protein kinases and phosphatases, which act coordinately in the regulation of signal transduction through the phosphorylation and dephosphorylation of target proteins, have been described to be key elements in ROS-mediated signaling events. The major mechanism by which these proteins may be modified by oxidation involves the presence of key redox-sensitive cysteine residues. Protein kinase C (PKC) is involved in a variety of cellular signaling pathways. These proteins have been shown to contain a unique structural feature that is susceptible to oxidative modification. A large number of scientific studies have highlighted the importance of ROS as a second messenger in numerous cellular processes, including cell proliferation, gene expression, adhesion, differentiation, senescence, and apoptosis. In this context, the goal of this review is to discuss the mechanisms by which PKCs are modulated by ROS and how these processes are involved in the cellular response.

No MeSH data available.


Related in: MedlinePlus

General mechanism of cell signaling activation through mitochondria/PKC/nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. In pathological conditions, a mitochondrial dysfunction could lead to an increase in reactive oxygen species (ROS) generation. ROS can directly trigger cell signaling or activate different PKC isoforms, depending on cell type and stimulation. Activated PKC stimulates NADPH oxidase, which generates ROS. These ROS could activate another group or the same group of PKCs in a feedback mechanism or induce cell signaling. Depending on the stimulus, it could lead to cell survival or death.
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f3-ijms-13-10697: General mechanism of cell signaling activation through mitochondria/PKC/nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. In pathological conditions, a mitochondrial dysfunction could lead to an increase in reactive oxygen species (ROS) generation. ROS can directly trigger cell signaling or activate different PKC isoforms, depending on cell type and stimulation. Activated PKC stimulates NADPH oxidase, which generates ROS. These ROS could activate another group or the same group of PKCs in a feedback mechanism or induce cell signaling. Depending on the stimulus, it could lead to cell survival or death.

Mentions: Because different PKC isoforms are present in a variety of cells and are involved in a number of signaling pathways, it is difficult to ascribe a common ROS-dependent mechanism for all PKC isotypes. However, it seems that under pathological conditions, a general signaling mechanism is triggered in mitochondrial dysfunction. In this context, an increase in ROS production by mitochondria activates local PKCs, which in turn activate Nox enzymes. Nox enzymes could also activate another group or the same group of PKCs in a feedback mechanism. Consequently, the redox state of the cell becomes imbalanced. Depending on the stimuli, proapoptotic signaling may occur through ROS activation of MAPK, such as SAPK/JNK, ERK1/2 and p38, or antiapoptotic signals ccould be triggered through activation of the NFκB or Akt/ASK1 pathway [177]. Figure 3 represents a general mechanism of cell signaling activation trough mitochondria/PKC/NADPH oxidase. This mechanism can be different depending on the cell and activation stimulus. More studies are necessary to elucidate the mechanisms that are involved in these signaling pathways.


Cell signaling through protein kinase C oxidation and activation.

Cosentino-Gomes D, Rocco-Machado N, Meyer-Fernandes JR - Int J Mol Sci (2012)

General mechanism of cell signaling activation through mitochondria/PKC/nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. In pathological conditions, a mitochondrial dysfunction could lead to an increase in reactive oxygen species (ROS) generation. ROS can directly trigger cell signaling or activate different PKC isoforms, depending on cell type and stimulation. Activated PKC stimulates NADPH oxidase, which generates ROS. These ROS could activate another group or the same group of PKCs in a feedback mechanism or induce cell signaling. Depending on the stimulus, it could lead to cell survival or death.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3472709&req=5

f3-ijms-13-10697: General mechanism of cell signaling activation through mitochondria/PKC/nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. In pathological conditions, a mitochondrial dysfunction could lead to an increase in reactive oxygen species (ROS) generation. ROS can directly trigger cell signaling or activate different PKC isoforms, depending on cell type and stimulation. Activated PKC stimulates NADPH oxidase, which generates ROS. These ROS could activate another group or the same group of PKCs in a feedback mechanism or induce cell signaling. Depending on the stimulus, it could lead to cell survival or death.
Mentions: Because different PKC isoforms are present in a variety of cells and are involved in a number of signaling pathways, it is difficult to ascribe a common ROS-dependent mechanism for all PKC isotypes. However, it seems that under pathological conditions, a general signaling mechanism is triggered in mitochondrial dysfunction. In this context, an increase in ROS production by mitochondria activates local PKCs, which in turn activate Nox enzymes. Nox enzymes could also activate another group or the same group of PKCs in a feedback mechanism. Consequently, the redox state of the cell becomes imbalanced. Depending on the stimuli, proapoptotic signaling may occur through ROS activation of MAPK, such as SAPK/JNK, ERK1/2 and p38, or antiapoptotic signals ccould be triggered through activation of the NFκB or Akt/ASK1 pathway [177]. Figure 3 represents a general mechanism of cell signaling activation trough mitochondria/PKC/NADPH oxidase. This mechanism can be different depending on the cell and activation stimulus. More studies are necessary to elucidate the mechanisms that are involved in these signaling pathways.

Bottom Line: In this context, protein kinases and phosphatases, which act coordinately in the regulation of signal transduction through the phosphorylation and dephosphorylation of target proteins, have been described to be key elements in ROS-mediated signaling events.The major mechanism by which these proteins may be modified by oxidation involves the presence of key redox-sensitive cysteine residues.These proteins have been shown to contain a unique structural feature that is susceptible to oxidative modification.

View Article: PubMed Central - PubMed

Affiliation: Institute of Medical Biochemistry, Federal University of Rio de Janeiro (UFRJ), CCS, Bloco H, Cidade Universitária, Ilha do Fundão, 21941-590, Rio de Janeiro, RJ, Brazil; E-Mails: rocco@bioqmed.ufrj.br (N.R.-M.); meyer@bioqmed.ufrj.br (J.R.M.-F.) ; Institute of National Science and Technology of Structural Biology and Bioimage (INCTBEB), CCS, Bloco H, Cidade Universitária, Ilha do Fundão, 21941-590, Rio de Janeiro, RJ, Brazil.

ABSTRACT
Due to the growing importance of cellular signaling mediated by reactive oxygen species (ROS), proteins that are reversibly modulated by these reactant molecules are of high interest. In this context, protein kinases and phosphatases, which act coordinately in the regulation of signal transduction through the phosphorylation and dephosphorylation of target proteins, have been described to be key elements in ROS-mediated signaling events. The major mechanism by which these proteins may be modified by oxidation involves the presence of key redox-sensitive cysteine residues. Protein kinase C (PKC) is involved in a variety of cellular signaling pathways. These proteins have been shown to contain a unique structural feature that is susceptible to oxidative modification. A large number of scientific studies have highlighted the importance of ROS as a second messenger in numerous cellular processes, including cell proliferation, gene expression, adhesion, differentiation, senescence, and apoptosis. In this context, the goal of this review is to discuss the mechanisms by which PKCs are modulated by ROS and how these processes are involved in the cellular response.

No MeSH data available.


Related in: MedlinePlus