S-Nitrosoglutathione Reductase Underlies the Dysfunctional Relaxation to Nitric Oxide in Preterm Labor

Overview

Journal Sci Rep

Specialty Science

Date 2018 Apr 6

PMID 29618799

Citations 11

Authors

Scott D Barnett

Christina R Smith

Craig C Ulrich

Josh E Baker

Iain L O Buxton

Affiliations

Soon will be listed here.

Abstract

Tocolytics show limited efficacy to prevent preterm delivery. In uterine smooth muscle cGMP accumulation following addition of nitric oxide (NO) has little effect on relaxation suggesting a role for protein S-nitrosation. In human myometrial tissues from women in labor at term (TL), or spontaneously in labor preterm (sPTL), direct stimulation of soluble guanylyl cyclase (sGC) fails to relax myometrium, while the same treatment relaxes vascular smooth muscle completely. Unlike term myometrium, effects of NO are not only blunted in sPTL, but global protein S-nitrosation is also diminished, suggesting a dysfunctional response to NO-mediated protein S-nitrosation. Examination of the enzymatic regulator of endogenous S-nitrosoglutathione availability, S-nitrosoglutathione reductase, reveals increased expression of the reductase in preterm myometrium associated with decreased total protein S-nitrosation. Blockade of S-nitrosoglutathione reductase relaxes sPTL tissue. Addition of NO donor to the actin motility assay attenuates force. Failure of sGC activation to mediate relaxation in sPTL tissues, together with the ability of NO to relax TL, but not sPTL myometrium, suggests a unique pathway for NO-mediated relaxation in myometrium. Our results suggest that examining the action of S-nitrosation on critical contraction associated proteins central to the regulation of uterine smooth muscle contraction can reveal new tocolytic targets.

Citing Articles

Facilitating Nitrite-Derived S-Nitrosothiol Formation in the Upper Gastrointestinal Tract in the Therapy of Cardiovascular Diseases.

Silva-Cunha M, Lacchini R, Tanus-Santos J Antioxidants (Basel). 2024; 13(6).

PMID: 38929130 PMC: 11200996. DOI: 10.3390/antiox13060691.

Multiple pregnancies, the myometrium and the role of mechanical factors in the timing of labour.

Arrowsmith S Curr Res Physiol. 2023; 6:100105.

PMID: 38107788 PMC: 10724211. DOI: 10.1016/j.crphys.2023.100105.

The combined uterorelaxant effect of sildenafil and terbutalin in the rat: The potential benefit of co-administration of low doses.

Barna T, Szucs K, Mirdamadi M, Gaspar R Heliyon. 2023; 9(12):e22488.

PMID: 38046168 PMC: 10686861. DOI: 10.1016/j.heliyon.2023.e22488.

β3 Receptor Signaling in Pregnant Human Myometrium Suggests a Role for β3 Agonists as Tocolytics.

Buxton I, Asif H, Barnett S Biomolecules. 2023; 13(6).

PMID: 37371585 PMC: 10296559. DOI: 10.3390/biom13061005.

Novel identification and modulation of the mechanosensitive Piezo1 channel in human myometrium.

Barnett S, Asif H, Buxton I J Physiol. 2022; 601(9):1675-1690.

PMID: 35941750 PMC: 9905381. DOI: 10.1113/JP283299.

References

Prince A, Antony K, Chu D, Aagaard K . The microbiome, parturition, and timing of birth: more questions than answers. J Reprod Immunol. 2014; 104-105:12-9. PMC: 4157949. DOI: 10.1016/j.jri.2014.03.006. View

Cleeter M, Cooper J, Darley-Usmar V, Moncada S, Schapira A . Reversible inhibition of cytochrome c oxidase, the terminal enzyme of the mitochondrial respiratory chain, by nitric oxide. Implications for neurodegenerative diseases. FEBS Lett. 1994; 345(1):50-4. DOI: 10.1016/0014-5793(94)00424-2. View

Muglia L, Katz M . The enigma of spontaneous preterm birth. N Engl J Med. 2010; 362(6):529-35. DOI: 10.1056/NEJMra0904308. View

Romero R, Dey S, Fisher S . Preterm labor: one syndrome, many causes. Science. 2014; 345(6198):760-5. PMC: 4191866. DOI: 10.1126/science.1251816. View

Ray K, Lorch S . Hospitalization of early preterm, late preterm, and term infants during the first year of life by gestational age. Hosp Pediatr. 2013; 3(3):194-203. DOI: 10.1542/hpeds.2012-0063. View

Wolhuter K, Eaton P . How widespread is stable protein S-nitrosylation as an end-effector of protein regulation?. Free Radic Biol Med. 2017; 109:156-166. DOI: 10.1016/j.freeradbiomed.2017.02.013. View

Chester M, Seedorf G, Tourneux P, Gien J, Tseng N, Grover T . Cinaciguat, a soluble guanylate cyclase activator, augments cGMP after oxidative stress and causes pulmonary vasodilation in neonatal pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol. 2011; 301(5):L755-64. PMC: 3213988. DOI: 10.1152/ajplung.00138.2010. View

Keller A, Nesvizhskii A, Kolker E, Aebersold R . Empirical statistical model to estimate the accuracy of peptide identifications made by MS/MS and database search. Anal Chem. 2002; 74(20):5383-92. DOI: 10.1021/ac025747h. View

Liu L, Yan Y, Zeng M, Zhang J, Hanes M, Ahearn G . Essential roles of S-nitrosothiols in vascular homeostasis and endotoxic shock. Cell. 2004; 116(4):617-28. DOI: 10.1016/s0092-8674(04)00131-x. View

10.

Buxton I, KAISER R, Malmquist N, Tichenor S . NO-induced relaxation of labouring and non-labouring human myometrium is not mediated by cyclic GMP. Br J Pharmacol. 2001; 134(1):206-14. PMC: 1572926. DOI: 10.1038/sj.bjp.0704226. View

11.

Lamont C, Jorgensen J, Lamont R . The safety of tocolytics used for the inhibition of preterm labour. Expert Opin Drug Saf. 2016; 15(9):1163-73. DOI: 10.1080/14740338.2016.1187128. View

12.

Kuenzli K, Bradley M, Buxton I . Cyclic GMP-independent effects of nitric oxide on guinea-pig uterine contractility. Br J Pharmacol. 1996; 119(4):737-43. PMC: 1915763. DOI: 10.1111/j.1476-5381.1996.tb15734.x. View

13.

Staab C, Alander J, Brandt M, Lengqvist J, Morgenstern R, Grafstrom R . Reduction of S-nitrosoglutathione by alcohol dehydrogenase 3 is facilitated by substrate alcohols via direct cofactor recycling and leads to GSH-controlled formation of glutathione transferase inhibitors. Biochem J. 2008; 413(3):493-504. DOI: 10.1042/BJ20071666. View

14.

Papatsonis D, Flenady V, Cole S, Liley H . Oxytocin receptor antagonists for inhibiting preterm labour. Cochrane Database Syst Rev. 2005; (3):CD004452. DOI: 10.1002/14651858.CD004452.pub2. View

15.

Whitworth M, Quenby S . Prophylactic oral betamimetics for preventing preterm labour in singleton pregnancies. Cochrane Database Syst Rev. 2008; (1):CD006395. PMC: 8923517. DOI: 10.1002/14651858.CD006395.pub2. View

16.

Cappelletti M, Della Bella S, Ferrazzi E, Mavilio D, Divanovic S . Inflammation and preterm birth. J Leukoc Biol. 2015; 99(1):67-78. DOI: 10.1189/jlb.3MR0615-272RR. View

17.

FURCHGOTT R . Endothelium-derived relaxing factor: discovery, early studies, and identification as nitric oxide. Biosci Rep. 1999; 19(4):235-51. DOI: 10.1023/a:1020537506008. View

18.

Tichenor S, Malmquist N, Buxton I . Dissociation of cGMP accumulation and relaxation in myometrial smooth muscle: effects of S-nitroso-N-acetylpenicillamine and 3-morpholinosyndonimine. Cell Signal. 2003; 15(8):763-72. DOI: 10.1016/s0898-6568(03)00006-8. View

19.

Erdmann E, Semigran M, Nieminen M, Gheorghiade M, Agrawal R, Mitrovic V . Cinaciguat, a soluble guanylate cyclase activator, unloads the heart but also causes hypotension in acute decompensated heart failure. Eur Heart J. 2012; 34(1):57-67. DOI: 10.1093/eurheartj/ehs196. View

20.

Nogueira L, Figueiredo-Freitas C, Casimiro-Lopes G, Magdesian M, Assreuy J, Sorenson M . Myosin is reversibly inhibited by S-nitrosylation. Biochem J. 2009; 424(2):221-31. DOI: 10.1042/BJ20091144. View