Please read Dr. Jude’s article in the American Journal of Respiratory Cell and Molecular Biology titled, “Starving a Cell Promotes Airway Smooth Muscle Relaxation: Inhibition of Glycolysis Attenuates Excitation-Contraction Coupling.“
The salient clinical feature of asthma, bronchospasm, is due primarily to agonist-induced airway smooth muscle (ASM) shortening. In ASM cells, the intracellular signaling cascades- collectively known as excitation-contraction (EC) coupling, evoke force generation. EC coupling can be semi-quantitatively assessed in HASM cells by measuring the markers-rise in cytosolic Ca2+, and phosphorylation of myosin light chain (MLC) and the regulatory subunit of myosin phosphatase (MYPT1). A variety of extrinsic and intrinsic factors modulate EC coupling in ASM cells to amplify AHR in asthma. Our previous studies showed that cytokines, toxicants, and allergens amplify EC coupling in ASM cells to mediate AHR. Recently we reported that human ASM (HASM) cells isolated from obese lung donors exhibited amplified contractile phenotype, characterized by elevated markers of EC coupling. However, the precise mechanisms driving amplified EC coupling in HASM cells remain poorly understood. Glucose catabolism generates energy and intermediate metabolites critical for cellular functions. Glycolysis is regulated by 3 rate-limiting enzymes, namely hexokinase, phosphofructokinase, and pyruvate kinase. To read the full article.
Starving a Cell Promotes Airway Smooth Muscle Relaxation: Inhibition of Glycolysis Attenuates Excitation-Contraction Coupling. Xu S, Karmacharya N, Woo J, Cao G, Guo C, Gow A, Panettieri RA Jr, Jude JA. Am J Respir Cell Mol Biol. 2022 Oct 13. PMID: 36227725 DOI: 1165/rcmb.2021-0495OC Online ahead of print.