Ukr.Biochem.J. 2019; Volume 91, Issue 4, Jul-Aug, pp. 33-40

doi: https://doi.org/10.15407/ubj91.04.033

Sources and regulation of nitric oxide synthesis in uterus smooth muscle cells

H. V. Danylovych, Yu. V. Danylovych, T. V. Bohach,
V. T. Hurska, S. O. Kosterin

Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: danylovych@biochem.kiev.ua

Received: 28 February 2019; Accepted: 17 May 2019

It was proved that NO synthesis in isolated mitochondria of rat uterus smooth muscle depended on the entry of exogenous Ca2+ to mitochondria (inhibited by 1-10 mM Mg2+ in the absence of ATP and by 10 μM ruthenium red) and was suppressed by calmodulin antagonists (0.1-10 μM calmidazolium and 1-100 μM trifluoperazine). It was blocked by NG-nitro-L-arginine, a known antagonist of the constitutive NO-synthase, with a half-maximal inhibition effect at about 25 μM. Moderate deholesterinization of the plasma membrane of myocytes after processing with 0.01% digitonin was followed by increased nitric oxide biosynthesis by cells. The data obtained suggested that mitochondria and plasmalemma is a possible source of NO synthesis in uterine myocytes.

Keywords: , , , ,


References:

  1. Ahmad A, Dempsey SK, Daneva Z, Azam M4, Li N, Li PL6, Ritter JK. Role of Nitric Oxide in the Cardiovascular and Renal Systems. Int J Mol Sci. 2018 Sep 3;19(9). pii: E2605. PubMed, PubMedCentral, CrossRef
  2. Zheng J, Zhai K, Chen Y, Zhang X, Miao L, Wei B, Ji G. Nitric oxide mediates stretch-induced Ca2+ oscillation in smooth muscle. J Cell Sci. 2016 Jun 15;129(12):2430-7. PubMed, CrossRef
  3. Buxton IL. Regulation of uterine function: a biochemical conundrum in the regulation of smooth muscle relaxation. Mol Pharmacol. 2004 May;65(5):1051-9. PubMed, CrossRef
  4. Sladek SM, Magness RR, Conrad KP. Nitric oxide and pregnancy. Am J Physiol. 1997 Feb;272(2 Pt 2):R441-63. PubMed, CrossRef
  5. Wetzka B, Schäfer WR, Stehmans A, Zahradnik HP. Effects of nitric oxide donors on the contractility and prostaglandin synthesis of myometrial strips from pregnant and non-pregnant women. Gynecol Endocrinol. 2001 Feb;15(1):34-42. PubMed, CrossRef
  6. Yamamura H, Kawasaki K, Inagaki S, Suzuki Y, Imaizumi Y. Local Ca2+ coupling between mitochondria and sarcoplasmic reticulum following depolarization in guinea pig urinary bladder smooth muscle cells. Am J Physiol Cell Physiol. 2018 Jan 1;314(1):C88-C98. PubMed, CrossRef
  7. Zaobornyj T, Ghafourifar P. Strategic localization of heart mitochondrial NOS: a review of the evidence. Am J Physiol Heart Circ Physiol. 2012 Dec 1;303(11):H1283-93. PubMed, CrossRef
  8. Dedkova EN, Blatter LA. Measuring mitochondrial function in intact cardiac myocytes. J Mol Cell Cardiol. 2012 Jan;52(1):48-61. PubMed, PubMedCentral, CrossRef
  9. Drumm BT, Rembetski BE, Cobine CA, Baker SA, Sergeant GP, Hollywood MA, Thornbury KD, Sanders KM. Ca2+ signalling in mouse urethral smooth muscle in situ: role of Ca2+ stores and Ca2+ influx mechanisms. J Physiol. 2018 Apr 15;596(8):1433-1466. PubMed, PubMedCentral, CrossRef
  10. Tatoyan A, Giulivi C. Purification and characterization of a nitric-oxide synthase from rat liver mitochondria. J Biol Chem. 1998 May 1;273(18):11044-8. PubMed, CrossRef
  11. Lores-Arnaiz S, D’Amico G, Czerniczyniec A, Bustamante J, Boveris A. Brain mitochondrial nitric oxide synthase: in vitro and in vivo inhibition by chlorpromazine. Arch Biochem Biophys. 2004 Oct 15;430(2):170-7. PubMed, CrossRef
  12. Alvarez S, Boveris A. Mitochondrial nitric oxide metabolism in rat muscle during endotoxemia. Free Radic Biol Med. 2004 Nov 1;37(9):1472-8. PubMed, CrossRef
  13. Boveris A, Valdez LB, Alvarez S, Zaobornyj T, Boveris AD, Navarro A. Kidney mitochondrial nitric oxide synthase. Antioxid Redox Signal. 2003 Jun;5(3):265-71. PubMed, CrossRef
  14. Bustamante J, Bersier G, Romero M, Badin RA, Boveris A. Nitric oxide production and mitochondrial dysfunction during rat thymocyte apoptosis. Arch Biochem Biophys. 2000 Apr 15;376(2):239-47. PubMed, CrossRef
  15. Danylovych HV, Danylovych YV, Gulina MO, Bohach TV, Kosterin SO. NO-synthase activity in mitochondria of uterus smooth muscle: identification and biochemical properties. Gen Physiol Biophys. 2019 Jan;38(1):39-50. PubMed, CrossRef
  16. Carreras MC, Poderoso JJ. Mitochondrial nitric oxide in the signaling of cell integrated responses. Am J Physiol Cell Physiol. 2007 May;292(5):C1569-80. PubMed, CrossRef
  17. Kolomiets OV, Danylovych IuV, Danylovych HV, Kosterin SO. Ca2+ accumulation study in isolated smooth muscle mitochondria using fluo-4 AM. Ukr Biokhim Zhurn. 2013 Jul-Aug;85(4):30-9. (In Ukrainian). PubMed, CrossRef
  18. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248-54. PubMed, CrossRef
  19. Mollard P, Mironneau J, Amedee T, Mironneau C. Electrophysiological characterization of single pregnant rat myometrial cells in short-term primary culture. Am J Physiol. 1986 Jan;250(1 Pt 1):C47-54. PubMed, CrossRef
  20. Pilchova I, Klacanova K, Tatarkova Z, Kaplan P, Racay P. The Involvement of Mg2+ in Regulation of Cellular and Mitochondrial Functions. Oxid Med Cell Longev. 2017;2017:6797460.  PubMed, PubMedCentral, CrossRef
  21. Boelens AD, Pradhan RK, Blomeyer CA, Camara AK, Dash RK, Stowe DF. Extra-matrix Mg2+ limits Ca2+ uptake and modulates Ca2+ uptake-independent respiration and redox state in cardiac isolated mitochondria. J Bioenerg Biomembr. 2013 Jun;45(3):203-18.  PubMed, PubMedCentral, CrossRef
  22. Kolomiets OV, Danylovych YuV., Danylovych GV. H+-Ca2+ Exchanger in the Myometrium Mitochondria: Modulation by Exogenous and Endogenous Compounds.  Int J Physiol Pathophys. 2015;6(4):287-297. CrossRef
  23. Welland A, Daff S. Conformation-dependent hydride transfer in neuronal nitric oxide synthase reductase domain. FEBS J. 2010 Sep;277(18):3833-43.  PubMed, CrossRef
  24. Veklich TO1, Kosterin SO, Shynlova OP. Cationic specificity of a Ca2+-accumulating system in smooth muscle cell mitochondria. Ukr Biokhim Zhurn. 2002 Jan-Feb;74(1):42-8. (In Ukrainian). PubMed
  25. Kone BC, Kuncewicz T, Zhang W, Yu ZY. Protein interactions with nitric oxide synthases: controlling the right time, the right place, and the right amount of nitric oxide. Am J Physiol Renal Physiol. 2003 Aug;285(2):F178-90. PubMed, CrossRef
  26. Sasaki T, Naka M, Nakamura F, Tanaka T. Ruthenium red inhibits the binding of calcium to calmodulin required for enzyme activation. J Biol Chem. 1992 Oct 25;267(30):21518-23. PubMed
  27. Babich LH, Shlykov SH, Naumova NV, Kosterin SO. Use of flow cytometry to determine Ca2+ content in mitochondria and influence of calmodulin antagonists on it. Ukr Biokhim Zhurn. 2008 Jul-Aug;80(4):51-8. (In Ukrainian). PubMed
  28. Kojima H, Nakatsubo N, Kikuchi K, Kawahara S, Kirino Y, Nagoshi H, Hirata Y, Nagano T. Detection and imaging of nitric oxide with novel fluorescent indicators: diaminofluoresceins. Anal Chem. 1998 Jul 1;70(13):2446-53. PubMed, CrossRef
  29. Campbell AK. Intracellular calcium. John Wiley & Sons, Ltd. 2015. CrossRef
  30. Shlykov SG, Babich LG, Kosterin SA. Suspension of digitonin-treated smooth muscle cells as model of the calcium pump of myometrial endoplasmic reticulum. Biochemistry (Mosc). 1997;62(12):1666-1671. (In Russian).
  31. Fiskum G. Intracellular levels and distribution of Ca2+ in digitonin-permeabilized cells. Cell Calcium. 1985 Apr;6(1-2):25-37. PubMed, CrossRef
  32. Durán WN, Breslin JW, Sánchez FA. The NO cascade, eNOS location, and microvascular permeability. Cardiovasc Res. 2010 Jul 15;87(2):254-61. PubMed, PubMedCentral, CrossRef
  33. Szydlarska J, Weiss C, Marycz K. The Effect of Methyl-β-cyclodextrin on Apoptosis, Proliferative Activity, and Oxidative Stress in Adipose-Derived Mesenchymal Stromal Cells of Horses Suffering from Metabolic Syndrome (EMS). Molecules. 2018 Jan 30;23(2). pii: E287. PubMed, PubMedCentral, CrossRef

Creative CommonsThis work is licensed under a Creative Commons Attribution 4.0 International License.