TY - JOUR
T1 - Comparative proteomics analysis reveals unique early signaling response of saccharomyces cerevisiae to oxidants with different mechanism of action
AU - Pandey, Prajita
AU - Zaman, Khadiza
AU - Prokai, Laszlo
AU - Shulaev, Vladimir
N1 - Funding Information:
Funding: This research was funded by an AERI Seed Grant (V.S.) and by The Welch Foundation (endowment BK-0031, L.P.).
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/1/1
Y1 - 2021/1/1
N2 - The early signaling events involved in oxidant recognition and triggering of oxidant-specific defense mechanisms to counteract oxidative stress still remain largely elusive. Our discovery driven comparative proteomics analysis revealed unique early signaling response of the yeast Saccharomyces cerevisiae on the proteome level to oxidants with a different mechanism of action as early as 3 min after treatment with four oxidants, namely H2O2, cumene hydroperoxide (CHP), and menadione and diamide, when protein abundances were compared using label-free quantification relying on a high-resolution mass analyzer (Orbitrap). We identified significant regulation of 196 proteins in response to H2O2, 569 proteins in response to CHP, 369 proteins in response to menadione and 207 proteins in response to diamide. Only 17 proteins were common across all treatments, but several more proteins were shared between two or three oxidants. Pathway analyses revealed that each oxidant triggered a unique signaling mechanism associated with cell survival and repair. Signaling pathways mostly regulated by oxidants were Ran, TOR, Rho, and eIF2. Furthermore, each oxidant regulated these pathways in a unique way indicating specificity of response to oxidants having different modes of action. We hypothesize that interplay of these signaling pathways may be important in recognizing different oxidants to trigger different downstream MAPK signaling cascades and to induce specific responses.
AB - The early signaling events involved in oxidant recognition and triggering of oxidant-specific defense mechanisms to counteract oxidative stress still remain largely elusive. Our discovery driven comparative proteomics analysis revealed unique early signaling response of the yeast Saccharomyces cerevisiae on the proteome level to oxidants with a different mechanism of action as early as 3 min after treatment with four oxidants, namely H2O2, cumene hydroperoxide (CHP), and menadione and diamide, when protein abundances were compared using label-free quantification relying on a high-resolution mass analyzer (Orbitrap). We identified significant regulation of 196 proteins in response to H2O2, 569 proteins in response to CHP, 369 proteins in response to menadione and 207 proteins in response to diamide. Only 17 proteins were common across all treatments, but several more proteins were shared between two or three oxidants. Pathway analyses revealed that each oxidant triggered a unique signaling mechanism associated with cell survival and repair. Signaling pathways mostly regulated by oxidants were Ran, TOR, Rho, and eIF2. Furthermore, each oxidant regulated these pathways in a unique way indicating specificity of response to oxidants having different modes of action. We hypothesize that interplay of these signaling pathways may be important in recognizing different oxidants to trigger different downstream MAPK signaling cascades and to induce specific responses.
KW - Antioxidants
KW - Global untargeted proteomics
KW - MAPK cascade
KW - Oxidative stress
KW - RAN signaling
KW - Reactive oxygen species
KW - TOR signaling
UR - http://www.scopus.com/inward/record.url?scp=85098788250&partnerID=8YFLogxK
U2 - 10.3390/ijms22010167
DO - 10.3390/ijms22010167
M3 - Article
C2 - 33375274
AN - SCOPUS:85098788250
SN - 1661-6596
VL - 22
SP - 1
EP - 17
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 1
M1 - 167
ER -