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Editorial
. 2023 Dec;69(6):605-607.
doi: 10.1165/rcmb.2023-0295ED.

Reactive Oxygen Species Behaving Badly: Oxidized Phosphatidylcholines Corrupt Ca2+ Signaling in Airway Smooth Muscle

Deepak A Deshpande  1 , Raymond B Penn  1
Affiliations
Editorial

Reactive Oxygen Species Behaving Badly: Oxidized Phosphatidylcholines Corrupt Ca2+ Signaling in Airway Smooth Muscle

Deepak A Deshpande et al. Am J Respir Cell Mol Biol. 2023 Dec.
No abstract available

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Figures

Figure 1.
Figure 1.
Intracellular signaling mechanisms for oxidized phosphatidylcholine–induced airway smooth muscle (ASM) contraction. Inhaled biological and chemical environmental factors can overwhelm intrinsic antioxidant pathways, resulting in accumulation of ROS, which oxidize biomolecules. This includes phosphatidylcholine (e.g., 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine [PAPC]), which is abundant in cell membranes and extracellular fluid such as lung surfactant. Oxidation generates myriad oxidized PAPC (OxPAPC) variants, which induce bronchial narrowing. In human ASM cells, OxPAPC triggers concomitant, but mutually exclusive, activation of the ryanodine receptor (RyR) and transient receptor potential ankyrin 1 (TRPA1) that mediates flux of Ca2+ from sarcoplasmic reticulum and extracellular stores, respectively, resulting in an acute and sustained increase in intracellular Ca2+. OxPAPC may activate TRPA1directly or indirectly, e.g., by altering cell membrane properties. RyR activation is dependent on cADPR, a product derived from NAD by cyclase activity of the ectoenzyme CD38, which can be induced by OxPAPC. These phases of mobilized Ca2+ work cooperatively, as both are required to induce ASM contraction. Inhibition of either pool is sufficient to prevent pMLC20, which is essential for activation of actomyosin cross-bridge cycling, after OxPAPC exposure, as well as for airway contraction in murine thin-cut lung slices. cADPR = cyclic ADP ribose; NAD = nicotinamide adenine dinucleotide; pMLC20 = phosphorylation of 20 kDa myosin light chain; ROS = reactive oxygen species.
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References

    1. Pascoe CD, Vaghasiya J, Halayko AJ. Oxidation specific epitopes in asthma: new possibilities for treatment. Int J Biochem Cell Biol . 2020;129:105864. - PubMed
    1. Pascoe CD, Roy N, Turner-Brannen E, Schultz A, Vaghasiya J, Ravandi A, et al. Oxidized phosphatidylcholines induce multiple functional defects in airway epithelial cells. Am J Physiol Lung Cell Mol Physiol . 2021;321:L703–L717. - PubMed
    1. Pascoe CD, Jha A, Ryu MH, Ragheb M, Vaghasiya J, Basu S, et al. Canadian Respiratory Research N. Allergen inhalation generates pro-inflammatory oxidised phosphatidylcholine associated with airway dysfunction. Eur Respir J . 2021;57:2000839. - PubMed
    1. Vaghasiya J, Dalvand A, Sikarwar A, Mangat D, Ragheb M, Kowatsch K, et al. Oxidized phosphatidylcholines trigger TRPA1 and ryanodine receptor–dependent airway smooth muscle contraction Am J Respir Cell Mol Biol 2023;69:649–665. - PubMed
    1. Prakash YS. Airway smooth muscle in airway reactivity and remodeling: what have we learned? Am J Physiol Lung Cell Mol Physiol . 2013;305:L912–L933. - PMC - PubMed

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