Cell Signaling Pathways activated by Hydrogen Peroxide

1. Mode of action of Pathway

The process of cell signaling through hydrogen peroxide is a very sensitive approach that initiates itself with determined pathways. This is a mode noted through redox signaling, where there are many receptors acting by the means of NADPH oxidase (NOX) in order to create reactive oxygen species, like those of superoxide radical (O₂−•) added by hydrogen peroxide (H₂O₂). This activity is subject to regulate determined action of signaling proteins like those of tyrosine phosphatases, led by transcription modes and ion channels. It is the O₂ −• participation in nitrosylation reaction that leads to determined Pathway 7.

2. Chronology of Cell Signaling Research

Period	Discovery	Significance	References
2005	Uterine Wnt/β-catenin signaling	to note early mode of embryo in cells exchange signals uterus' cells	Mohamed OA, Jonnaert M, Labelle-Dumais C, Kuroda K, Clarke HJ, Dufort D (June 2005). "Uterine Wnt/β-catenin signaling is required for implantation". Proc Natl Acad Sci U.S.A. 102 (24): 8579–84. doi:10.1073/pnas.0500612102. PMC 1150820.PMID 15930138.
2008	Retinoic Acid Synthesis	note paracrine signals like retinoic acid target for just cells within vicinity menat for emitting cell.	Duester G (September 2008). "Retinoic Acid Synthesis and Signaling during Early Organogenesis". Cell 134 (6): 921–31. doi:10.1016/j.cell.2008.09.002.PMC 2632951. PMID 18805086.
2009	Thrombospondin 2 Potentiates Notch3/Jagged1	identifications of features receptors for cell motility as well as differentiation	Meng H, Zhang X, Hankenson KD, Wang MM (2009-03-20). "Thrombospondin 2 Potentiates Notch3/Jagged1 Signaling". J Biol Chem 284 (12): 7866–74.doi:10.1074/jbc.M803650200. PMC 2658079. PMID 19147503.
2011	Move of Proteins	illustration of long-ranged allostery being necessary for features of cell signaling events	Bu Z, Callaway DJ (2011). "Proteins MOVE! Protein dynamics and long-range allostery in cell signaling". Advances in Protein Chemistry and Structural Biology. Advances in Protein Chemistry and Structural Biology 83: 163–221. doi:10.1016/B978-0-12-381262-9.00005-7. ISBN 978-0-12-381262-9. PMID 21570668.

3. Cell Signaling

According to the investigations led by Bae, et.al. (1999) there is a possible role led by reactive oxygen species (or the ROS) in the activation of p70(S6k) that remains as the core approach in cells’ progression from G(0)/G(1) to S phase in the cell cycle through translational up-regulation of mRNA transcripts, that is liable to encode protein synthetic machinery based components. Treatment led over mouse epidermal cell that id JB6 with H(2)O(2) initiated extra cellularly aspect through glucose or the glucose oxidase for the activation of p70(S6k) added by p90(Rsk) along with phosphorylation meant for p42(MAPK)/p44(MAPK). p70(S6k) activation and p90(Rsk) activation are dose-dependent as well as transient. There are maximal activities in extracts that were treated for a span of 15 and 30 min. Moreover, featurization of ROS-induced formulation of p70(S6k) gets implied towards specific inhibitors related to p70(S6k) mode of signaling pathway, whereby rapamycin added by wortmannin get revealed so that ROS acted upstream under rapamycin-sensitive composition FRAP/RAFT as well as wortmannin-sensitive composition phosphatidylinositol 3-kinase, due to inhibitors led by inhibiting ROS-induced p70(S6k) actions. Further, Ca(2+) chelation is also subject to get inhibited by ROS-induced activation under p70(S6k), that indicates Ca(2+) being a mediator for the functionalities of p70(S6k) activation through ROS. Still, down-regulation meant through 12-O-tetradecanoylphorbol-13-acetate (or the TPA)-responsive protein kinase C (PKC) through the provision of chronic pretreatment added by TPA/determined PKC inhibitor Ro-31-8220 never  block p70(S6k) activation through ROS. This notes that TPA-responsive activation PKC is not necessary for stimulation of p70(S6k) through hydrogen peroxide or H(2)O(2) in terms of JB6 cells. There are exposure made over JB6 cells that meant towards platelet attained from growth/epidermal growth under rapid increase noted for H(2)O(2), phosphorylation, along with p70(S6k) activation that antagonize pretreatment of catalase. This research of Bae, et.al. (1999) suggests that activity of ROS as messenger in terms of growth factor is liable to induce p70(S6k) signaling pathway.

4. Illustration of Pathways

As a matter of fact Cells evolve through a sophisticated mechanism under intracellular mode of signalling that is noted through localized changes within state of oxidation of determined proteins. Cells’ internal environment generally gets highly reduced. There are some forms of stress related to the mode of increase in state of oxidation and the same can induce apoptosis. There are still some phagocytic cells, like neutrophils is rapidly generated superoxide radical (O2−•) as well as hydrogen peroxide (H₂O₂), which are liable to kill other kinds of cells in the inflammatory responses. Further, these pathological effects are having more evidence towards redox system as adapted through the performance of varied signaling functionalities. This is capable of modulating activity through other signaling pathways. This is the reason that they are capable of controlling various cellular processes, added by cell proliferation, cellular senescence and apoptosis. Few of such effects get exerted by two-way interaction manage with Ca₂+ signaling (Chiarugi and Cirri, 2003). As for instance, redox signaling can promote events under tyrosine phosphorylation is liable to generate diversified signaling cascades and the same is modulating in respect to activity under ryanodine receptors (or the RYRs) along with inositol 1,4,5-trisphosphate receptors (or as noted by InsP3Rs), releasing Ca₂+ . As against this, Ca₂+ is liable to stimulate redox signaling, especially inside mitochondrion, that indicates that there are dynamic modes of interactions that operate among these signaling pathways. Two basic sorts of redox signaling are reactive oxygen species (or the ROS) signaling that depends over the creation of ROS; and reactive nitrogen species (or the RNS) signaling carried through RNS and further is connected to nitric oxide (or the NO) or pathway of cyclic GMP signaling. See the image below-

5. Hydrogen peroxide (H2O2)

There is a huge demand about the implication of hydrogen peroxide (or H₂O₂) as the same appears to remain as the primary messenger molecule that is liable to function within the pathway of redox signaling. As the same got no unpaired electrons, the role of H₂O₂ is never free radical and therefore is never specifically considered as a powerful oxidizing agent. This refers to that the functionalities are in being a messenger through the process of diffusing from respective action site in order to interact with more distant targets (Rhee, et.al. 2005). Still, the relevant influencing sphere gets restricted through short half life that determines under the rapid reactive oxygen species (or the ROS) metabolism related to H₂O_2. Since the paracrine signal diffuses away from respective stimulated cells in respect to alter neighbouring cells’ activity. There is the release of H₂O₂  in the process of healing of wound that recruits leucocytes being integral to inflammatory response.

6. Conclusion

Eventually, it can be stated that oxidative stress remains significant mode for the damage of the cell in association with initiation, followed by progression of diversified diseases. As a result, all sorts of air-living organisms are inclusive of antioxidant enzymes, limiting oxidative stress through species of detoxifying reactive oxygen added by hydrogen peroxide. Still, in reference to eukaryotes, the role of hydrogen peroxide is vital as it is the core component in the process of regulation varied modes of biological proceedings (Mikkelsen and Wardman, 2003). It is the molecular mechanisms through which the hydrogen peroxide remains sensible and relevantly increases in evidence, which the antioxidant enzymes act under multiple approaches. In this process, the sensors as well as regulators related to signal transduction act in reference to the actions of hydrogen peroxide.

Sources:

Bae GU, Seo DW, Kwon HK, Lee HY, Hong S, Lee ZW, Ha KS, Lee HW, Han JW. (1999) Hydrogen peroxide activates p70(S6k) signaling pathway. J Biol Chem. 1999 Nov 12;274 (46):32596-602.

Chiarugi, P. and Cirri, P. (2003) Redox egulation of tyrosine phosphatases during receptor tyrosine kinase signal transduction. Trends Biochem. Sci. 28:509–514.

Mikkelsen, R.B. and Wardman, P. (2003) Biological chemistry of reactive oxygen and nitrogen and radiation-induced signal transduction mechanisms. Oncogene 22:5734–5754.

Molecular and Neuroanatomical Findings in Bipolar Disorder. http://www.discoverymedicine.com/R-H-Belmaker/files/2009/08/belmaker_26_tab1.jpg (Retrieved on 31st March, 2013)

Rhee, S.G., Kang, S.W., Jeong, W., Chang, T.-S., Yang, K.-S. and Woo, H.A. (2005) Intracellular messenger function of hydrogen peroxide and its regulation by peroxyredoxins. Curr. Opin. Cell Biol. 17:183–189.