Hypochlorous acid facilitates inducible nitric oxide synthase subunit dissociation : The link between heme destruction, disturbance of the zinc-tetrathiolate center, and the prevention by melatonin
Copyright © 2022 Elsevier Inc. All rights reserved..
Inducible nitric oxide synthase (iNOS) is a zinc-containing hemoprotein composed of two identical subunits, each containing a reductase and an oxygenase domain. The reductase domain contains binding sites for NADPH, FAD, FMN, and tightly bound calmodulin and the oxygenase domain contains binding sites for heme, tetrahydrobiopterin (H4B), and l-arginine. The enzyme converts l-arginine into nitric oxide (NO) and citrulline in the presence of O2. It has previously been demonstrated that myeloperoxidase (MPO), which catalyzes formation of hypochlorous acid (HOCl) from hydrogen peroxide (H2O2) and chloride (Cl-), is enhanced in inflammatory diseases and could be a potent scavenger of NO. Using absorbance spectroscopy and gel filtration chromatography, we investigated the role of increasing concentrations of HOCl in mediating iNOS heme destruction and subsequent subunit dissociation and unfolding. The results showed that dimer iNOS dissociation between 15 and 100 μM HOCl was accompanied by loss of heme content and NO synthesis activity. The dissociated subunits-maintained cytochrome c and ferricyanide reductase activities. There was partial unfolding of the subunits at 300 μM HOCl and above, and the subunit unfolding transition was accompanied by loss of reductase activities. These events can be prevented when the enzyme is preincubated with melatonin prior to HOCl addition. Melatonin supplementation to patients experiencing low NO levels due to inflammatory diseases may be helpful to restore physiological NO functions.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2022 |
|---|---|
| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:124 |
|---|---|
| Enthalten in: |
Nitric oxide : biology and chemistry - 124(2022) vom: 01. Juli, Seite 32-38 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Camp, Olivia G [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 09.06.2022 Date Revised 30.06.2022 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.niox.2022.04.006 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM340418729 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM340418729 | ||
| 003 | DE-627 | ||
| 005 | 20231226005159.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2022 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.niox.2022.04.006 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1134.xml |
| 035 | |a (DE-627)NLM340418729 | ||
| 035 | |a (NLM)35513289 | ||
| 035 | |a (PII)S1089-8603(22)00050-7 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Camp, Olivia G |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Hypochlorous acid facilitates inducible nitric oxide synthase subunit dissociation |b The link between heme destruction, disturbance of the zinc-tetrathiolate center, and the prevention by melatonin |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 09.06.2022 | ||
| 500 | |a Date Revised 30.06.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2022 Elsevier Inc. All rights reserved. | ||
| 520 | |a Inducible nitric oxide synthase (iNOS) is a zinc-containing hemoprotein composed of two identical subunits, each containing a reductase and an oxygenase domain. The reductase domain contains binding sites for NADPH, FAD, FMN, and tightly bound calmodulin and the oxygenase domain contains binding sites for heme, tetrahydrobiopterin (H4B), and l-arginine. The enzyme converts l-arginine into nitric oxide (NO) and citrulline in the presence of O2. It has previously been demonstrated that myeloperoxidase (MPO), which catalyzes formation of hypochlorous acid (HOCl) from hydrogen peroxide (H2O2) and chloride (Cl-), is enhanced in inflammatory diseases and could be a potent scavenger of NO. Using absorbance spectroscopy and gel filtration chromatography, we investigated the role of increasing concentrations of HOCl in mediating iNOS heme destruction and subsequent subunit dissociation and unfolding. The results showed that dimer iNOS dissociation between 15 and 100 μM HOCl was accompanied by loss of heme content and NO synthesis activity. The dissociated subunits-maintained cytochrome c and ferricyanide reductase activities. There was partial unfolding of the subunits at 300 μM HOCl and above, and the subunit unfolding transition was accompanied by loss of reductase activities. These events can be prevented when the enzyme is preincubated with melatonin prior to HOCl addition. Melatonin supplementation to patients experiencing low NO levels due to inflammatory diseases may be helpful to restore physiological NO functions | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Hypochlorous acid | |
| 650 | 4 | |a Inflammation | |
| 650 | 4 | |a Melatonin | |
| 650 | 4 | |a Nitric oxide synthase | |
| 650 | 4 | |a Tetrahydrobiopterin | |
| 650 | 4 | |a Zinc | |
| 650 | 7 | |a Nitric Oxide |2 NLM | |
| 650 | 7 | |a 31C4KY9ESH |2 NLM | |
| 650 | 7 | |a Heme |2 NLM | |
| 650 | 7 | |a 42VZT0U6YR |2 NLM | |
| 650 | 7 | |a Hypochlorous Acid |2 NLM | |
| 650 | 7 | |a 712K4CDC10 |2 NLM | |
| 650 | 7 | |a Arginine |2 NLM | |
| 650 | 7 | |a 94ZLA3W45F |2 NLM | |
| 650 | 7 | |a Hydrogen Peroxide |2 NLM | |
| 650 | 7 | |a BBX060AN9V |2 NLM | |
| 650 | 7 | |a Oxidoreductases |2 NLM | |
| 650 | 7 | |a EC 1.- |2 NLM | |
| 650 | 7 | |a Oxygenases |2 NLM | |
| 650 | 7 | |a EC 1.13.- |2 NLM | |
| 650 | 7 | |a Nitric Oxide Synthase |2 NLM | |
| 650 | 7 | |a EC 1.14.13.39 |2 NLM | |
| 650 | 7 | |a Nitric Oxide Synthase Type II |2 NLM | |
| 650 | 7 | |a EC 1.14.13.39 |2 NLM | |
| 650 | 7 | |a Zinc |2 NLM | |
| 650 | 7 | |a J41CSQ7QDS |2 NLM | |
| 650 | 7 | |a Melatonin |2 NLM | |
| 650 | 7 | |a JL5DK93RCL |2 NLM | |
| 700 | 1 | |a Bai, David |e verfasserin |4 aut | |
| 700 | 1 | |a Awonuga, Awoniyi |e verfasserin |4 aut | |
| 700 | 1 | |a Goud, Pravin T |e verfasserin |4 aut | |
| 700 | 1 | |a Abu-Soud, Husam M |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Nitric oxide : biology and chemistry |d 1998 |g 124(2022) vom: 01. Juli, Seite 32-38 |w (DE-627)NLM093851162 |x 1089-8611 |7 nnns |
| 773 | 1 | 8 | |g volume:124 |g year:2022 |g day:01 |g month:07 |g pages:32-38 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.niox.2022.04.006 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 124 |j 2022 |b 01 |c 07 |h 32-38 | ||