PMID- 31506428
OWN - NLM
STAT- MEDLINE
DCOM- 20200730
LR  - 20231013
IS  - 2041-4889 (Electronic)
VI  - 10
IP  - 9
DP  - 2019 Sep 10
TI  - Lactate and pyruvate promote oxidative stress resistance through hormetic ROS 
      signaling.
PG  - 653
LID - 10.1038/s41419-019-1877-6 [doi]
LID - 653
AB  - L-lactate was long considered a glycolytic by-product but is now being recognized 
      as a signaling molecule involved in cell survival. In this manuscript, we report 
      the role of L-lactate in stress resistance and cell survival mechanisms using 
      neuroblastoma cells (SH-SY5Y) as well as the C. elegans model. We observed that 
      L-lactate promotes cellular defense mechanisms, including Unfolded Protein 
      Response (UPR) and activation of nuclear factor erythroid 2-related factor 2 
      (NRF2), by promoting a mild Reactive Oxygen Species (ROS) burst. This increase in 
      ROS triggers antioxidant defenses and pro-survival pathways, such as PI3K/AKT and 
      Endoplasmic Reticulum (ER) chaperones. These results contribute to the 
      understanding of the molecular mechanisms involved in beneficial effects of 
      L-lactate, involving mild ROS burst, leading to activation of unfolded protein 
      responses and detoxification mechanisms. We present evidence that this hormetic 
      mechanism induced by L-lactate protects against oxidative stress in vitro and in 
      vivo. This work contributes to the identification of molecular mechanisms, which 
      could serve as targets for future therapeutic approaches for cell protection and 
      aging-related disorders.
FAU - Tauffenberger, Arnaud
AU  - Tauffenberger A
AUID- ORCID: 0000-0003-0207-9659
AD  - Laboratory for Cellular Imaging and Energetics, Biological and Environmental 
      Sciences and Engineering Division, King Abdullah University of Science and 
      Technology, Thuwal, Saudi Arabia. arnaud.tauffenberger@kaust.edu.sa.
FAU - Fiumelli, Hubert
AU  - Fiumelli H
AD  - Laboratory for Cellular Imaging and Energetics, Biological and Environmental 
      Sciences and Engineering Division, King Abdullah University of Science and 
      Technology, Thuwal, Saudi Arabia.
FAU - Almustafa, Salam
AU  - Almustafa S
AD  - Laboratory for Cellular Imaging and Energetics, Biological and Environmental 
      Sciences and Engineering Division, King Abdullah University of Science and 
      Technology, Thuwal, Saudi Arabia.
AD  - Imam Abdulrahman bin Faisal University, Dammam, Saudi Arabia.
FAU - Magistretti, Pierre J
AU  - Magistretti PJ
AD  - Laboratory for Cellular Imaging and Energetics, Biological and Environmental 
      Sciences and Engineering Division, King Abdullah University of Science and 
      Technology, Thuwal, Saudi Arabia. pierre.magistretti@kaust.edu.sa.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190910
PL  - England
TA  - Cell Death Dis
JT  - Cell death & disease
JID - 101524092
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (NFE2L2 protein, human)
RN  - 0 (Reactive Oxygen Species)
RN  - 33X04XA5AT (Lactic Acid)
RN  - 8558G7RUTR (Pyruvic Acid)
SB  - IM
MH  - Cell Line, Tumor
MH  - Humans
MH  - Lactic Acid/*pharmacology
MH  - NF-E2-Related Factor 2/metabolism
MH  - Oxidative Stress/*drug effects
MH  - Pyruvic Acid/*pharmacology
MH  - Reactive Oxygen Species/*metabolism
MH  - Signal Transduction/*drug effects
MH  - Unfolded Protein Response/drug effects
PMC - PMC6737085
COIS- The authors declare that they have no conflict of interest.
EDAT- 2019/09/12 06:00
MHDA- 2020/07/31 06:00
PMCR- 2019/09/10
CRDT- 2019/09/12 06:00
PHST- 2019/04/10 00:00 [received]
PHST- 2019/08/01 00:00 [accepted]
PHST- 2019/07/17 00:00 [revised]
PHST- 2019/09/12 06:00 [entrez]
PHST- 2019/09/12 06:00 [pubmed]
PHST- 2020/07/31 06:00 [medline]
PHST- 2019/09/10 00:00 [pmc-release]
AID - 10.1038/s41419-019-1877-6 [pii]
AID - 1877 [pii]
AID - 10.1038/s41419-019-1877-6 [doi]
PST - epublish
SO  - Cell Death Dis. 2019 Sep 10;10(9):653. doi: 10.1038/s41419-019-1877-6.