Neuroprotective effects of extracellular <scp>DJ</scp>‐1 on reperfusion injury in <scp>SH</scp>‐<scp>SY</scp>5<scp>Y</scp> cells

Han, Jay J.; Luk, Beryl; Lee, Frank J.S.

doi:10.1002/syn.21963

Cited by 7 publications

(8 citation statements)

References 32 publications

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“…Also, some reports suggest extracellular activities for DJ-1. It is secreted under several pathological conditions including breast cancer (Le Naour et al, 2001), Parkinson's disease (Maita et al, 2008;Tsuboi et al, 2008) or stroke (Allard et al, 2005), and a protective role against ischemia (Kaneko et al, 2014) and I/R (Han et al, 2017). Likewise, we have reported endothelial DJ-1 secretion under ischemia and I/R, and evidenced its effects on endothelial cell function at reperfusion, thereby suggesting a role in regulating cardiac injury .…”

Section: Introductionsupporting

confidence: 69%

DJ-1 administration exerts cardioprotection in a mouse model of acute myocardial infarction

et al. 2022

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Cardiovascular diseases, and particularly acute myocardial infarction (MI), are the most common causes of death worldwide. Infarct size is the major predictor of clinical outcomes in MI. The Parkinson’s disease associated protein, DJ-1 (also known as PARK7), is a multifunctional protein with chaperone, redox sensing and mitochondrial homeostasis activities. Previously, we provided the evidence for a central role of endogenous DJ-1 in the cardioprotection of post-conditioning. In the present study, we tested the hypothesis that systemic administration of recombinant DJ-1 exerts cardioprotective effects in a mouse model of MI and also explored the associated transcriptional response. We report a significant treatment-induced reduction in infarct size, leukocyte infiltration, apoptosis and oxidative stress. Effects potentially mediated by G-protein-coupled receptor signaling and modulation of the immune response. Collectively, our results indicate a protective role for the exogenously administrated DJ-1 upon MI, and provide the first line of evidence for an extracellular activity of DJ-1 regulating cardiac injury in vivo.

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Section: Introductionsupporting

confidence: 69%

DJ-1 administration exerts cardioprotection in a mouse model of acute myocardial infarction

et al. 2022

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“…Besides the ability to act at the cytosolic level, the protein has also been suggested to be protective in the extracellular compartment. Indeed, extracellularly applied DJ-1 has been shown to rescue neuroblastoma cells exposed to oxygen-glucose deprivation, although the precise mechanism remains elusive [ 163 ]. In this regard, the secreted form of the protein has been found in oxygen-glucose deprived human neural progenitor cells [ 150 ], supporting a role of the protein in the extracellular milieu.…”

Section: The Involvement Of Dj-1 In Ir Injurymentioning

confidence: 99%

DJ-1: A promising therapeutic candidate for ischemia-reperfusion injury

et al. 2021

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DJ-1 is a multifaceted protein with pleiotropic functions that has been implicated in multiple diseases, ranging from neurodegeneration to cancer and ischemia-reperfusion injury. Ischemia is a complex pathological state arising when tissues and organs do not receive adequate levels of oxygen and nutrients. When the blood flow is restored, significant damage occurs over and above that of ischemia alone and is termed ischemia-reperfusion injury. Despite great efforts in the scientific community to ameliorate this pathology, its complex nature has rendered it challenging to obtain satisfactory treatments that translate to the clinic. In this review, we will describe the recent findings on the participation of the protein DJ-1 in the pathophysiology of ischemia-reperfusion injury, firstly introducing the features and functions of DJ-1 and, successively highlighting the therapeutic potential of the protein.

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“…14,15 Particularly, this cell line is used to develop the in vitro OGD/IR model. [15][16][17][18][19][20][21] Current findings in regenerative medicine have strengthened the search for new stem cell sources with beneficial properties; in particular, amniotic fluid has been identified as a valid resource of stem cells in this field. Adult stem cells, even after reprogramming, could preserve epigenetic alterations, thus representing a limitation in their application.…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, since SH‐SY5Y cells are human‐derived, they express several human‐specific proteins and isoforms that would not be inherently present in rodent primary cultures 14,15 . Particularly, this cell line is used to develop the in vitro OGD/IR model 15‐21 …”

Section: Introductionmentioning

confidence: 99%

Neuroprotective effects of human amniotic fluid stem cells-derived secretome in an ischemia/reperfusion model

Castelli

Antonucci

Tessitore

et al. 2020

Stem Cells Translational Medicine

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Stem cells offer the basis for the promotion of robust new therapeutic approaches for a variety of human disorders. There are still many limitations to be overcome before clinical therapeutic application, including a better understanding of the mechanism by which stem cell therapies may lead to enhanced recovery. In vitro investigations are necessary to dissect the mechanisms involved and to support the potential development in stem cell-based therapies. In spite of growing interest in human amniotic fluid stem cells, not much is known about the characteristics of their secretome and regarding the potential neuroprotective mechanism in different pathologies, including stroke. To get more insight on amniotic fluid cells therapeutic potential, signal transduction pathways activated by human amniotic fluid stem cells (hAFSCs)derived secretome in a stroke in vitro model (ischemia/reperfusion [I/R] model) were investigated by Western blot. Moreover, miRNA expression in the exosomal fraction of the conditioned medium was analyzed. hAFSCs-derived secretome was able to activate prosurvival and anti-apoptotic pathways. MicroRNA analysis in the exosomal component revealed a panel of 16 overexpressed miRNAs involved in the regulation of coherent signaling pathways. In particular, the pathways of relevance in ischemia/reperfusion, such as neurotrophin signaling, and those related to neuroprotection and neuronal cell death, were analyzed. The results obtained strongly point toward the neuroprotective effects of the hAFSCs-conditioned medium in the in vitro stroke model here analyzed. This can be achieved by the modulation and activation of pro-survival processes, at least in part, due to the activity of secreted miRNAs.

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Neuroprotective effects of extracellular DJ‐1 on reperfusion injury in SH‐SY5Y cells

Cited by 7 publications

References 32 publications

DJ-1 administration exerts cardioprotection in a mouse model of acute myocardial infarction

DJ-1 administration exerts cardioprotection in a mouse model of acute myocardial infarction

DJ-1: A promising therapeutic candidate for ischemia-reperfusion injury

Neuroprotective effects of human amniotic fluid stem cells-derived secretome in an ischemia/reperfusion model

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