H2S contributed from CSE during cellular senescence suppresses inflammation and nitrosative stress
Copyright © 2022 Elsevier B.V. All rights reserved..
Aging involves the time-dependent deterioration of physiological functions attributed to various intracellular and extracellular factors. Cellular senescence is akin to aging and involves alteration in redox homeostasis. This is primarily marked by increased reactive oxygen/nitrogen species (ROS/RNS), inflammatory gene expression, and senescence-associated beta-galactosidase activity, all hallmarks of aging. It is proposed that gasotransmitters which include hydrogen sulfide (H2S), carbon monoxide (CO), and nitric oxide (NO), may affect redox homeostasis during senescence. H2S has been independently shown to induce DNA damage and suppress oxidative stress. While an increase in NO levels during aging is well established, the role of H2S has remained controversial. To understand the role of H2S during aging, we evaluated H2S homeostasis in non-senescent and senescent cells, using a combination of direct measurements with a fluorescent reporter dye (WSP-5) and protein sulfhydration analysis. The free intracellular H2S and total protein sulfhydration levels are high during senescence, concomitant to cystathionine gamma-lyase (CSE) expression induction. Using lentiviral shRNA-mediated expression knockdown, we identified that H2S contributed by CSE alters global gene expression, which regulates key inflammatory processes during cellular senescence. We propose that H2S decreases inflammation during cellular senescence by reducing phosphorylation of IκBα and the p65 subunit of nuclear factor kappa B (NF-κB). H2S was also found to reduce NO levels, a significant source of nitrosative stress during cellular senescence. Overall, we establish H2S as a key gasotransmitter molecule that regulates inflammatory phenotype and nitrosative stress during cellular senescence.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:1870 |
|---|---|
| Enthalten in: |
Biochimica et biophysica acta. Molecular cell research - 1870(2023), 2 vom: 31. Feb., Seite 119388 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Gupta, Kavya [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 04.01.2023 Date Revised 17.02.2023 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.bbamcr.2022.119388 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM348856288 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM348856288 | ||
| 003 | DE-627 | ||
| 005 | 20231226041246.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.bbamcr.2022.119388 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1162.xml |
| 035 | |a (DE-627)NLM348856288 | ||
| 035 | |a (NLM)36372112 | ||
| 035 | |a (PII)S0167-4889(22)00180-X | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Gupta, Kavya |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a H2S contributed from CSE during cellular senescence suppresses inflammation and nitrosative stress |
| 264 | 1 | |c 2023 | |
| 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 04.01.2023 | ||
| 500 | |a Date Revised 17.02.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2022 Elsevier B.V. All rights reserved. | ||
| 520 | |a Aging involves the time-dependent deterioration of physiological functions attributed to various intracellular and extracellular factors. Cellular senescence is akin to aging and involves alteration in redox homeostasis. This is primarily marked by increased reactive oxygen/nitrogen species (ROS/RNS), inflammatory gene expression, and senescence-associated beta-galactosidase activity, all hallmarks of aging. It is proposed that gasotransmitters which include hydrogen sulfide (H2S), carbon monoxide (CO), and nitric oxide (NO), may affect redox homeostasis during senescence. H2S has been independently shown to induce DNA damage and suppress oxidative stress. While an increase in NO levels during aging is well established, the role of H2S has remained controversial. To understand the role of H2S during aging, we evaluated H2S homeostasis in non-senescent and senescent cells, using a combination of direct measurements with a fluorescent reporter dye (WSP-5) and protein sulfhydration analysis. The free intracellular H2S and total protein sulfhydration levels are high during senescence, concomitant to cystathionine gamma-lyase (CSE) expression induction. Using lentiviral shRNA-mediated expression knockdown, we identified that H2S contributed by CSE alters global gene expression, which regulates key inflammatory processes during cellular senescence. We propose that H2S decreases inflammation during cellular senescence by reducing phosphorylation of IκBα and the p65 subunit of nuclear factor kappa B (NF-κB). H2S was also found to reduce NO levels, a significant source of nitrosative stress during cellular senescence. Overall, we establish H2S as a key gasotransmitter molecule that regulates inflammatory phenotype and nitrosative stress during cellular senescence | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Cellular senescence | |
| 650 | 4 | |a Gasotransmitters | |
| 650 | 4 | |a Hydrogen sulfide | |
| 650 | 4 | |a Inflammation | |
| 650 | 4 | |a Nitric oxide | |
| 650 | 4 | |a Reactive oxygen species | |
| 650 | 7 | |a Hydrogen Sulfide |2 NLM | |
| 650 | 7 | |a YY9FVM7NSN |2 NLM | |
| 650 | 7 | |a NF-kappa B |2 NLM | |
| 650 | 7 | |a Nitric Oxide |2 NLM | |
| 650 | 7 | |a 31C4KY9ESH |2 NLM | |
| 650 | 7 | |a Reactive Oxygen Species |2 NLM | |
| 650 | 7 | |a Cystathionine gamma-Lyase |2 NLM | |
| 650 | 7 | |a EC 4.4.1.1 |2 NLM | |
| 700 | 1 | |a Mathew, Abraham Binoy |e verfasserin |4 aut | |
| 700 | 1 | |a Chakrapani, Harinath |e verfasserin |4 aut | |
| 700 | 1 | |a Saini, Deepak Kumar |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Biochimica et biophysica acta. Molecular cell research |d 2017 |g 1870(2023), 2 vom: 31. Feb., Seite 119388 |w (DE-627)NLM264216326 |x 1879-2596 |7 nnns |
| 773 | 1 | 8 | |g volume:1870 |g year:2023 |g number:2 |g day:31 |g month:02 |g pages:119388 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.bbamcr.2022.119388 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 1870 |j 2023 |e 2 |b 31 |c 02 |h 119388 | ||