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| Home > Articles > Published articles > Comparative Proteomics Unveils LRRFIP1 as a New Player in the DAPK1 Interactome of Neurons Exposed to Oxygen and Glucose Deprivation |
| Home > Articles > Published articles > Comparative Proteomics Unveils LRRFIP1 as a New Player in the DAPK1 Interactome of Neurons Exposed to Oxygen and Glucose Deprivation |
(Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol) (Institut Germans Trias i Pujol) (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol) (Universitat de València. Unidad Mitxa de Investigación Cerebrovascular) (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol) (Institut Germans Trias i Pujol)
| Date: | 2020 |
| Abstract: | Death-associated protein kinase 1 (DAPK1) is a pleiotropic hub of a number of networked distributed intracellular processes. Among them, DAPK1 is known to interact with the excitotoxicity driver NMDA receptor (NMDAR), and in sudden pathophysiological conditions of the brain, e. g. , stroke, several lines of evidence link DAPK1 with the transduction of glutamate-induced events that determine neuronal fate. In turn, DAPK1 expression and activity are known to be affected by the redox status of the cell. To delineate specific and differential neuronal DAPK1 interactors in stroke-like conditions in vitro, we exposed primary cultures of rat cortical neurons to oxygen/glucose deprivation (OGD), a condition that increases reactive oxygen species (ROS) and lipid peroxides. OGD or control samples were co-immunoprecipitated separately, trypsin-digested, and proteins in the interactome identified by high-resolution LC-MS/MS. Data were processed and curated using bioinformatics tools. OGD increased total DAPK1 protein levels, cleavage into shorter isoforms, and dephosphorylation to render the active DAPK1 form. The DAPK1 interactome comprises some 600 proteins, mostly involving binding, catalytic and structural molecular functions. OGD up-regulated 190 and down-regulated 192 candidate DAPK1-interacting proteins. Some differentially up-regulated interactors related to NMDAR were validated by WB. In addition, a novel differential DAPK1 partner, LRRFIP1, was further confirmed by reverse Co-IP. Furthermore, LRRFIP1 levels were increased by pro-oxidant conditions such as ODG or the ferroptosis inducer erastin. The present study identifies novel partners of DAPK1, such as LRRFIP1, which are suitable as targets for neuroprotection. |
| Grants: | Ministerio de Ciencia e Innovación SAF2010-22122 Instituto de Salud Carlos III RD16-0019-0020 Instituto de Salud Carlos III RD16-0019-0008 Agència de Gestió d'Ajuts Universitaris i de Recerca SGR1520 Agència de Gestió d'Ajuts Universitaris i de Recerca 2019PROD00120 |
| Note: | Altres ajuts: The group has received funding from 'la Caixa Foundation' CI15-00009, from the European Institute of Innovation and Technology (EIT) PoC-2016-SPAIN-04, which receives support from the European Union's Horizon 2020 research and innovation program, and from the 'Fundación para la Innovación y la Prospectiva en Salud en España (FIPSE)' program 3594-18. |
| Rights: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.  |
| Language: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Subject: | LRRFIP1 ; DAPK1 ; Neuron ; OGD ; MCAO ; NMDA ; ROS ; Ferroptosis |
| Published in: | Antioxidants, Vol. 9 Núm. 12 (2020) , p. 1202, ISSN 2076-3921 |
