Dataset Information

H2O2 induced oxidative stress may trigger cellular senescence in retinal photoreceptor cells through modulation of ECM-receptor interaction, oxidative phosphorylation and spliceosome pathways

ABSTRACT: Photoreceptor cells are highly susceptible to oxidative stress induced damage due to their high metabolic rate. Oxidative stress plays a key role in driving pathological events in several different ocular diseases which lead to retinal degeneration and ultimately blindness. A growing number of studies have been performed to understand downstream events caused by ROS induced oxidative stress in photoreceptor cells; however, the underlying mechanisms of ROS toxicity are not fully understood. Therefore, to shed light on the ROS induced downstream pathological events, we employed a tandem mass tag (TMT) labeling-based quantitative mass-spectrometric approach to determine proteome changes in 661W photoreceptor cells following oxidative stress induction via application of different concentrations of H2O2 at different time points. Overall, 5920 proteins were identified and quantified and 450 differentially expressed proteins (DEPs) were identified, which were altered in a dose and time dependent manner in all treatment groups compared to the control group. These proteins were involved in several biological pathways including spliceosome and ribosome response, activated glutathione metabolism, decreased ECM-receptor interaction, oxidative phosphorylation, abnormally regulated lysosome, apoptosis, and ribosome biogenesis. Our results highlighted ECM-receptor interaction, oxidative phosphorylation and spliceosome pathways as the major targets of oxidative stress that might mediate vascular dysfunction and cellular senescence.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Cell Culture, Eye Photoreceptor Cell

DISEASE(S): Eye Degenerative Disease

SUBMITTER: Liting Deng

LAB HEAD: Paul A. Haynes

PROVIDER: PXD037329 | Pride | 2023-05-10

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

Items per page:

1 - 5 of 54

Publications

Oxidative Stress Induced Dysfunction of Protein Synthesis in 661W Mice Photoreceptor Cells.

Deng Liting L Gupta Vivek V Abyadeh Morteza M Chitranshi Nitin N Pushpitha Kanishka K Wu Yunqi Y Gupta Veer V You Yuyi Y Paulo Joao A JA Graham Stuart L SL Mirzaei Mehdi M Haynes Paul A PA

Proteomes 20230403 2

Photoreceptor cells are highly susceptible to oxidative-stress-induced damage due to their high metabolic rate. Oxidative stress plays a key role in driving pathological events in several different ocular diseases, which lead to retinal degeneration and ultimately blindness. A growing number of studies have been performed to understand downstream events caused by ROS induced oxidative stress in photoreceptor cells; however, the underlying mechanisms of ROS toxicity are not fully understood. To s ...[more]

PMID: 37092453

Similar Datasets

Project description:Poly(ADP-ribose) Polymerase 1 (PARP-1) is a nuclear enzyme that catalyse the transfer of ADP-ribose units from NAD+ to several target proteins involved in cellular stress responses. Using the cell line WRL68, we have previously shown that the activation of PARP-1 induced by oxidative stress after H2O2 treatment lead to depletion of cellular NAD+ and ATP, which promote cell death. In this work, we used LC-MS/MS based phosphoproteomics to show that the oxidative damage induced by H2O2 treatment modified the phosphorylation of several proteins in WRL68 cells, most of them related to transcription process. Interestingly, genetic or pharmacological inhibition of PARP-1 reduced the phosphorylation of YAP1, a transcriptional coactivator involved in cell survival, in WRL68 cells after H2O2 treatment. Inhibition of PARP-1 increased cell viability after oxidative treatment and diminished the degradation of YAP1; the elimination of YAP1 by gene silencing abrogated the protective effect of PARP-1 inhibition, indicating that YAP1 is important for the survival of WRL68 cells after oxidative damage. In the same way, the supplementation of NAD+, substrate of PARP-1, on WRL68 cells suffering oxidative damage reduced the phosphorylation of YAP1, suggesting that the loss of cellular NAD+ caused by PARP-1 activation after oxidative treatment is responsible for the phosphorylation of YAP1. Finally, PARP-1 silencing after oxidative treatment diminished the activation of AMPK, a master regulator of cell metabolism implicated in the restoration of energy balance during metabolic stress. Since NAD+ supplementation reduced the phosphorylation of some AMPK substrates in WRL68 cells after oxidative treatment, we hypothesize that the loss of cellular NAD+ after PARP-1 activation may induce a metabolic stress that activates AMPK. In summary, we showed a new crucial role of PARP-1 in the response to oxidative stress in WRL68 cells; PARP-1 activation reduces the cell viability by promoting the phosphorylation and degradation of YAP1, which is mediated by the energy stress caused by PARP-1 activation.

			Action	DRS
	661W_TMT1_1.raw	Raw
	661W_TMT1_10.raw	Raw
	661W_TMT1_11.raw	Raw
	661W_TMT1_12.raw	Raw
	661W_TMT1_13.raw	Raw