TY  - JOUR
AU  - Živanović, Jasmina
AU  - Kouroussis, Emilia
AU  - Kohl, Joshua B.
AU  - Adhikari, Bikash
AU  - Bursać, Biljana
AU  - Schott-Roux, Sonia
AU  - Petrović, Dunja
AU  - Miljković, Jan Lj.
AU  - Thomas-Lopez, Daniel
AU  - Jung, Youngeun
AU  - Miler, Marko
AU  - Mitchell, Sarah
AU  - Milošević, Verica
AU  - Gomes, Jose Eduardo
AU  - Benhar, Moran
AU  - Gonzales-Zorn, Bruno
AU  - Ivanović-Burmazović, Ivana
AU  - Torregrossa, Roberta
AU  - Mitchell, James R.
AU  - Whiteman, Matthew
AU  - Schwarz, Guenter
AU  - Snyder, Solomon H.
AU  - Paul, Bindu D.
AU  - Carroll, Kate S.
AU  - Filipović, Miloš R.
PY  - 2019
UR  - https://www.sciencedirect.com/science/article/abs/pii/S1550413119305625
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3518
AB  - Life on Earth emerged in a hydrogen sulfide (H2S)-rich environment eons ago and with it protein persulfidation mediated by H2S evolved as a signaling mechanism. Protein persulfidation (S-sulfhydration) is a post-translational modification of reactive cysteine residues, which modulate protein structure and/or function. Persulfides are difficult to label and study due to their reactivity and similarity with cysteine. Here, we report a facile strategy for chemoselective persulfide bioconjugation using dimedone-based probes, to achieve highly selective, rapid, and robust persulfide labeling in biological samples with broad utility. Using this method, we show persulfidation is an evolutionarily conserved modification and waves of persulfidation are employed by cells to resolve sulfenylation and prevent irreversible cysteine overoxidation preserving protein function. We report an age-associated decline in persulfidation that is conserved across evolutionary boundaries. Accordingly, dietary or pharmacological interventions to increase persulfidation associate with increased longevity and improved capacity to cope with stress stimuli.
T2  - Cell Metabolism
T1  - Selective Persulfide Detection Reveals Evolutionarily Conserved Antiaging Effects of S-Sulfhydration
IS  - 6
VL  - 30
DO  - 10.1016/J.CMET.2019.10.007
SP  - 1152
EP  - 1170.e13
ER  - 

@article{
author = "Živanović, Jasmina and Kouroussis, Emilia and Kohl, Joshua B. and Adhikari, Bikash and Bursać, Biljana and Schott-Roux, Sonia and Petrović, Dunja and Miljković, Jan Lj. and Thomas-Lopez, Daniel and Jung, Youngeun and Miler, Marko and Mitchell, Sarah and Milošević, Verica and Gomes, Jose Eduardo and Benhar, Moran and Gonzales-Zorn, Bruno and Ivanović-Burmazović, Ivana and Torregrossa, Roberta and Mitchell, James R. and Whiteman, Matthew and Schwarz, Guenter and Snyder, Solomon H. and Paul, Bindu D. and Carroll, Kate S. and Filipović, Miloš R.",
year = "2019",
abstract = "Life on Earth emerged in a hydrogen sulfide (H2S)-rich environment eons ago and with it protein persulfidation mediated by H2S evolved as a signaling mechanism. Protein persulfidation (S-sulfhydration) is a post-translational modification of reactive cysteine residues, which modulate protein structure and/or function. Persulfides are difficult to label and study due to their reactivity and similarity with cysteine. Here, we report a facile strategy for chemoselective persulfide bioconjugation using dimedone-based probes, to achieve highly selective, rapid, and robust persulfide labeling in biological samples with broad utility. Using this method, we show persulfidation is an evolutionarily conserved modification and waves of persulfidation are employed by cells to resolve sulfenylation and prevent irreversible cysteine overoxidation preserving protein function. We report an age-associated decline in persulfidation that is conserved across evolutionary boundaries. Accordingly, dietary or pharmacological interventions to increase persulfidation associate with increased longevity and improved capacity to cope with stress stimuli.",
journal = "Cell Metabolism",
title = "Selective Persulfide Detection Reveals Evolutionarily Conserved Antiaging Effects of S-Sulfhydration",
number = "6",
volume = "30",
doi = "10.1016/J.CMET.2019.10.007",
pages = "1152-1170.e13"
}

Živanović, J., Kouroussis, E., Kohl, J. B., Adhikari, B., Bursać, B., Schott-Roux, S., Petrović, D., Miljković, J. Lj., Thomas-Lopez, D., Jung, Y., Miler, M., Mitchell, S., Milošević, V., Gomes, J. E., Benhar, M., Gonzales-Zorn, B., Ivanović-Burmazović, I., Torregrossa, R., Mitchell, J. R., Whiteman, M., Schwarz, G., Snyder, S. H., Paul, B. D., Carroll, K. S.,& Filipović, M. R.. (2019). Selective Persulfide Detection Reveals Evolutionarily Conserved Antiaging Effects of S-Sulfhydration. in Cell Metabolism, 30(6), 1152-1170.e13.
https://doi.org/10.1016/J.CMET.2019.10.007

Živanović J, Kouroussis E, Kohl JB, Adhikari B, Bursać B, Schott-Roux S, Petrović D, Miljković JL, Thomas-Lopez D, Jung Y, Miler M, Mitchell S, Milošević V, Gomes JE, Benhar M, Gonzales-Zorn B, Ivanović-Burmazović I, Torregrossa R, Mitchell JR, Whiteman M, Schwarz G, Snyder SH, Paul BD, Carroll KS, Filipović MR. Selective Persulfide Detection Reveals Evolutionarily Conserved Antiaging Effects of S-Sulfhydration. in Cell Metabolism. 2019;30(6):1152-1170.e13.
doi:10.1016/J.CMET.2019.10.007 .

Živanović, Jasmina, Kouroussis, Emilia, Kohl, Joshua B., Adhikari, Bikash, Bursać, Biljana, Schott-Roux, Sonia, Petrović, Dunja, Miljković, Jan Lj., Thomas-Lopez, Daniel, Jung, Youngeun, Miler, Marko, Mitchell, Sarah, Milošević, Verica, Gomes, Jose Eduardo, Benhar, Moran, Gonzales-Zorn, Bruno, Ivanović-Burmazović, Ivana, Torregrossa, Roberta, Mitchell, James R., Whiteman, Matthew, Schwarz, Guenter, Snyder, Solomon H., Paul, Bindu D., Carroll, Kate S., Filipović, Miloš R., "Selective Persulfide Detection Reveals Evolutionarily Conserved Antiaging Effects of S-Sulfhydration" in Cell Metabolism, 30, no. 6 (2019):1152-1170.e13,
https://doi.org/10.1016/J.CMET.2019.10.007 . .

TY  - CONF
AU  - Živanović, Jasmina
AU  - Kouroussis, Emilia
AU  - Kohl, Joshua
AU  - Miler, Marko
AU  - Mitchell, Sarah
AU  - Mitchell, James
AU  - Schwartz, Guenter
AU  - Milošević, Verica
AU  - Filipović R., Miloš
PY  - 2019
UR  - https://www.bcp.fu-berlin.de/en/biologie/arbeitsgruppen/mikrobiologie/ag_antelmann/meetings/190915_redox_res/Flyer-Sant-Feliu-2019-final6.pdf
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6039
AB  - For couple of decades aging is believed to be a consequence of damages accumulated by increased production of reactive oxygen species (ROS). Opposite to that, dietary restriction attempts to extend life have been linked to increased H2S production. We hypothesized that reacting with sulfenic acids (formed by ROS) H2S would rescue cysteine residue by forming persulfides. Persulfides are better ROS scavengers and could form protein S-sulfonates that could be cleaved back by disulfide reductase to restore free thiolate. This rescue loop would thus prevent irreversible thiol hyperoxidation. Using dimedone switch method we could first show that persulfidation is a posttranslational modification that is evolutionarily conserved (bacteria, flies, worms, mice and humans). Then we could also observe that thioredoxin readily catalyzes the reduction of cysteine S-sulfonate, two orders of magnitude faster than the reduction of corresponding disulfide. The persulfidation levels/H2S producing ability positively correlated with the ability of yeast, worms and mammalian cells to resist stress caused by ROS. Persulfidation declines with aging in worms, rats and mice, due to the downregulation of H2S producing enzymes, but dietary restriction in mice and worms restores persulfide levels and improves their lifespan. Based on these data we suggest that persulfidation represents an evolutionarily conserved anti-aging mechanism.
PB  - Berlin: Freie Universität Berlin
C3  - SPP1710 Conference: Thiol-based switches and redox regulation - from microbes to men; 2019 Sep 15-20; Sant Feliu de Guixols, Spain
T1  - Protein Persulfidation Protects Against Aging
SP  - 169
EP  - 169
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6039
ER  - 

@conference{
author = "Živanović, Jasmina and Kouroussis, Emilia and Kohl, Joshua and Miler, Marko and Mitchell, Sarah and Mitchell, James and Schwartz, Guenter and Milošević, Verica and Filipović R., Miloš",
year = "2019",
abstract = "For couple of decades aging is believed to be a consequence of damages accumulated by increased production of reactive oxygen species (ROS). Opposite to that, dietary restriction attempts to extend life have been linked to increased H2S production. We hypothesized that reacting with sulfenic acids (formed by ROS) H2S would rescue cysteine residue by forming persulfides. Persulfides are better ROS scavengers and could form protein S-sulfonates that could be cleaved back by disulfide reductase to restore free thiolate. This rescue loop would thus prevent irreversible thiol hyperoxidation. Using dimedone switch method we could first show that persulfidation is a posttranslational modification that is evolutionarily conserved (bacteria, flies, worms, mice and humans). Then we could also observe that thioredoxin readily catalyzes the reduction of cysteine S-sulfonate, two orders of magnitude faster than the reduction of corresponding disulfide. The persulfidation levels/H2S producing ability positively correlated with the ability of yeast, worms and mammalian cells to resist stress caused by ROS. Persulfidation declines with aging in worms, rats and mice, due to the downregulation of H2S producing enzymes, but dietary restriction in mice and worms restores persulfide levels and improves their lifespan. Based on these data we suggest that persulfidation represents an evolutionarily conserved anti-aging mechanism.",
publisher = "Berlin: Freie Universität Berlin",
journal = "SPP1710 Conference: Thiol-based switches and redox regulation - from microbes to men; 2019 Sep 15-20; Sant Feliu de Guixols, Spain",
title = "Protein Persulfidation Protects Against Aging",
pages = "169-169",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6039"
}

Živanović, J., Kouroussis, E., Kohl, J., Miler, M., Mitchell, S., Mitchell, J., Schwartz, G., Milošević, V.,& Filipović R., M.. (2019). Protein Persulfidation Protects Against Aging. in SPP1710 Conference: Thiol-based switches and redox regulation - from microbes to men; 2019 Sep 15-20; Sant Feliu de Guixols, Spain
Berlin: Freie Universität Berlin., 169-169.
https://hdl.handle.net/21.15107/rcub_ibiss_6039

Živanović J, Kouroussis E, Kohl J, Miler M, Mitchell S, Mitchell J, Schwartz G, Milošević V, Filipović R. M. Protein Persulfidation Protects Against Aging. in SPP1710 Conference: Thiol-based switches and redox regulation - from microbes to men; 2019 Sep 15-20; Sant Feliu de Guixols, Spain. 2019;:169-169.
https://hdl.handle.net/21.15107/rcub_ibiss_6039 .

Živanović, Jasmina, Kouroussis, Emilia, Kohl, Joshua, Miler, Marko, Mitchell, Sarah, Mitchell, James, Schwartz, Guenter, Milošević, Verica, Filipović R., Miloš, "Protein Persulfidation Protects Against Aging" in SPP1710 Conference: Thiol-based switches and redox regulation - from microbes to men; 2019 Sep 15-20; Sant Feliu de Guixols, Spain (2019):169-169,
https://hdl.handle.net/21.15107/rcub_ibiss_6039 .

TY  - CONF
AU  - Živanović, Jasmina
AU  - Kouroussis, Emilia
AU  - Miler, Marko
AU  - Schott-Roux, Sonia
AU  - Jarić, Ivana
AU  - Jakovljević, Vladimir
AU  - Milošević, Verica
AU  - Filipović R., Miloš
PY  - 2018
UR  - http://physiology.org.rs/4thCPS.php
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5926
AB  - An oxidative-posttranslational modification of thiols called protein persulfidation
(RSSH) represents the underlying mechanism of biological actions ascribed to new gasotransmitter hydrogen sulfide (H2S). We developed a new dimedone based method for detection of protein persulfidation and its selectivity was tested and confirmed in various experimental models (D. melanogaster, C. elegans, M. musculus. human cell lines and samples). Obtained results demonstrated that persulfidation represents an evolutionary conserved modification that correlates to the H2S production capacity and is accompanied with numerous physiological implications. One of such general observations is that persulfidation represents protective mechanism for the reduction of sulfenic acids under conditions of oxidative stress. When C. elegans mutants for CSE and MST were exposed to different oxidative stress inducers they showed enhanced sensitivity, while pretreatment with H2S donors rescued them. Additionally, we observed a strong correlation between protein persulfidation levels and development and aging in different experimental models. Fluctuations in the level of persultides were observed during development of C. elegans with prominent increase in L3 larval stage. Our data showed that after strong peak in L3, persulfide levels decreases during life in C. elegans. Decline of persulfide levels in the adult worms of different age was also observed. Similar effect was discovered in the brains of rats of different age. Immunobistological analysis of brain sections for H2S producing enzymes revealed the decrease in intensity of immunopositivity during aging process. Our results strongly propose protein persullidation represents a rescue loop from cysteine hyper-oxidation and subsequent loss of protein function. This general mechanism represents a promising tool in overcoming the consequences of increased oxidative stress during aging process.
PB  - Belgrade: Serbian Physiological Society
C3  - Abstract book: 4th Congress of Physiological Sciences of Serbia with International Participation: Current Trends in Physiological Sciences : from cell signals to the biology of aging; 2018 Sep 19-23; Niš, Serbia
T1  - Anti-aging properties of protein persulfidation
SP  - 143
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5926
ER  - 

@conference{
author = "Živanović, Jasmina and Kouroussis, Emilia and Miler, Marko and Schott-Roux, Sonia and Jarić, Ivana and Jakovljević, Vladimir and Milošević, Verica and Filipović R., Miloš",
year = "2018",
abstract = "An oxidative-posttranslational modification of thiols called protein persulfidation
(RSSH) represents the underlying mechanism of biological actions ascribed to new gasotransmitter hydrogen sulfide (H2S). We developed a new dimedone based method for detection of protein persulfidation and its selectivity was tested and confirmed in various experimental models (D. melanogaster, C. elegans, M. musculus. human cell lines and samples). Obtained results demonstrated that persulfidation represents an evolutionary conserved modification that correlates to the H2S production capacity and is accompanied with numerous physiological implications. One of such general observations is that persulfidation represents protective mechanism for the reduction of sulfenic acids under conditions of oxidative stress. When C. elegans mutants for CSE and MST were exposed to different oxidative stress inducers they showed enhanced sensitivity, while pretreatment with H2S donors rescued them. Additionally, we observed a strong correlation between protein persulfidation levels and development and aging in different experimental models. Fluctuations in the level of persultides were observed during development of C. elegans with prominent increase in L3 larval stage. Our data showed that after strong peak in L3, persulfide levels decreases during life in C. elegans. Decline of persulfide levels in the adult worms of different age was also observed. Similar effect was discovered in the brains of rats of different age. Immunobistological analysis of brain sections for H2S producing enzymes revealed the decrease in intensity of immunopositivity during aging process. Our results strongly propose protein persullidation represents a rescue loop from cysteine hyper-oxidation and subsequent loss of protein function. This general mechanism represents a promising tool in overcoming the consequences of increased oxidative stress during aging process.",
publisher = "Belgrade: Serbian Physiological Society",
journal = "Abstract book: 4th Congress of Physiological Sciences of Serbia with International Participation: Current Trends in Physiological Sciences : from cell signals to the biology of aging; 2018 Sep 19-23; Niš, Serbia",
title = "Anti-aging properties of protein persulfidation",
pages = "143",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5926"
}

Živanović, J., Kouroussis, E., Miler, M., Schott-Roux, S., Jarić, I., Jakovljević, V., Milošević, V.,& Filipović R., M.. (2018). Anti-aging properties of protein persulfidation. in Abstract book: 4th Congress of Physiological Sciences of Serbia with International Participation: Current Trends in Physiological Sciences : from cell signals to the biology of aging; 2018 Sep 19-23; Niš, Serbia
Belgrade: Serbian Physiological Society., 143.
https://hdl.handle.net/21.15107/rcub_ibiss_5926

Živanović J, Kouroussis E, Miler M, Schott-Roux S, Jarić I, Jakovljević V, Milošević V, Filipović R. M. Anti-aging properties of protein persulfidation. in Abstract book: 4th Congress of Physiological Sciences of Serbia with International Participation: Current Trends in Physiological Sciences : from cell signals to the biology of aging; 2018 Sep 19-23; Niš, Serbia. 2018;:143.
https://hdl.handle.net/21.15107/rcub_ibiss_5926 .

Živanović, Jasmina, Kouroussis, Emilia, Miler, Marko, Schott-Roux, Sonia, Jarić, Ivana, Jakovljević, Vladimir, Milošević, Verica, Filipović R., Miloš, "Anti-aging properties of protein persulfidation" in Abstract book: 4th Congress of Physiological Sciences of Serbia with International Participation: Current Trends in Physiological Sciences : from cell signals to the biology of aging; 2018 Sep 19-23; Niš, Serbia (2018):143,
https://hdl.handle.net/21.15107/rcub_ibiss_5926 .