Avid Bioservices Inc (CDMO)

[biopharm]

This involves phospholipid signaling in cell death pathways; nitric oxide(NO) interactions with cellular components including posttranslational modification of proteins and NO signaling...

NO signaling = Nitric Oxide signaling... and again, how will NO play a role in possibly some form of biomarker for detecting the amount of flipped PS ??

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Nitric Oxide Dissociates Lipid Oxidation from Apoptosis and Phosphatidylserine Externalization during Oxidative Stress†

James P. Fabisiak ,*‡
Vladimir A. Tyurin ,‡§
Yulia Y. Tyurina ,‡§
Andrey Sedlov ,‡
John S. Lazo ,? and
Valerian E. Kagan ‡?

Department of Environmental and Occupational Health, School of Public Health, RIDC Park, 260 Kappa Drive, University of Pittsburgh, Pittsburgh, Pennsylvania 15238, and Department of Pharmacology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15261
Biochemistry, 2000, 39 (1), pp 127–138
DOI: 10.1021/bi9912544
Publication Date (Web): December 8, 1999
Copyright © 2000 American Chemical Society

Oxidative stress in biological membranes can regulate various aspects of apoptosis, including phosphatidylserine (PS) externalization. It is not known, however, if the targets for these effects are lipids or proteins. Nitric oxide (NO), a bifunctional modulator of apoptosis, has both antioxidant and prooxidant potential. We report here that the NO donor PAPANONOate completely protected all phospholipids, including PS, from oxidation in HL-60 cells treated with 2,2‘-azobis(2,4-dimethylisovaleronitrile) (AMVN), presumably via the ability of NO to react with lipid-derived peroxyl radicals and terminate the propagation of lipid peroxidation. PAPANONOate, however, had no effect on PS externalization or other markers of apoptosis following AMVN. Therefore, PS oxidation is not required for PS externalization during AMVN-induced apoptosis. PS externalization was accompanied by inhibition of aminophospholipid translocase (APT). NO potentiated AMVN inhibition of APT. Treatment with PAPANONOate alone produced modest (20%) inhibition of APT without PS externalization. NO did not reverse AMVN-induced oxidation of glutathione and protein thiols. We speculate that APT was sensitive to AMVN and/or NO via modification of protein thiols critical for functional activity. Therefore, the lipoprotective effects of NO were insufficient to prevent PS externalization and apoptosis following oxidative stress. Other targets such as protein thiols may be important redox-sensitive regulators of apoptosis initiation and execution. Thus, in the absence of significant peroxynitrite formation, NO's antioxidant effects are restricted to protection of lipids, while modification of protein substrates continues to occur.

http://pubs.acs.org/doi/abs/10.1021/bi9912544?journalCode=bichaw

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Interesting seeing that exhaled NO was actually used as an endpoint...

Twenty adult, polysensitized subjects with seasonal and perennial allergic rhinitis who chose to undergo allergen immunotherapy were enrolled. They were evaluated at baseline, and 4, 8, 12, 24, and 52 weeks later. Exhaled nitric oxide was reported as the mean of triplicate determinations.

http://www.ncbi.nlm.nih.gov/pubmed/23958488

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http://www.dermnetnz.org/pathology/nitric-oxide.html