Tat-indoleamine 2,3-dioxygenase 1 elicits neuroprotective effects on ischemic injury

Abstract

It is well known that oxidative stress participates in neuronal cell death caused production of reactive oxygen species (ROS). The increased ROS is a major contributor to the development of ischemic injury. Indoleamine 2,3-dioxygenase 1 (IDO-1) is involved in the kynurenine pathway in tryptophan metabolism and plays a role as an anti-oxidant. However, whether IDO-1 would inhibit hippocampal cell death is poorly known. Therefore, we explored the effects of cell permeable Tat-IDO-1 protein against oxidative stress-induced HT-22 cells and in a cerebral ischemia/reperfusion injury model. Transduced Tat-IDO-1 reduced cell death, ROS production, and DNA fragmentation and inhibited mitogen-activated protein kinases (MAPKs) activation in H2O2 exposed HT-22 cells. In the cerebral ischemia/ reperfusion injury model, Tat-IDO-1 transduced into the brain and passing by means of the blood-brain barrier (BBB) significantly prevented hippocampal neuronal cell death. These results suggest that Tat-IDO-1 may present an alternative strategy to improve from the ischemic injury. [BMB Reports 2020; 53(11): 582-587]

Alcohol extract of Rubia yunnanensis: Metabolic alterations and preventive effects against OGD/R‑induced oxidative damage in HT22 cells

“…The current study found that the metabolite with the most significant change in levels among the aforementioned metabolites was tryptophan, which plays a key role in cerebral ischemia. IDO enzymes are the main rate-limiting enzymes for tryptophan degradation ( 23 ). IDO enzymes consist of two members, IDO1 and IDO2.…”

“…In addition, it is well known that the MAPK (p38, ERK and JNK) signaling pathways are highly associated with oxidative stress-induced cell death ( 24-26 ). It has been reported that Tat-IDO-1 transduced into HT22 cells reduces cell death, ROS production, DNA fragmentation and H 2 O 2 -induced MAPK phosphorylation ( 23 ). Other studies have also shown that overexpression of IDO proteins inhibits the activation of MAPK signaling pathways under conditions of oxidative stress ( 66 , 67 ).…”

“…The metabolite with the most significant difference following RY-A treatment was tryptophan. Indoleamine 2,3-dioxygenase is one of the major rate-limiting enzymes of the tryptophan-kynurenine pathway, which catalyzes the production of kynurenine from the essential amino acid L-tryptophan in mammalian extrahepatic tissues to exert an antioxidant effect (23). The signaling pathways of MAPKs (p38, ERK and JNK) have been highly correlated with oxidative stress-induced cell death (24)(25)(26).…”

Can kynurenine pathway be considered as a next-generation therapeutic target for Parkinson's disease? An update information

“…As a key enzyme in the KP, IDO1 plays a crucial role in the regulation of the KP. Hence, IDO1 should be considered a potential therapeutic target for neurological diseases (39).…”

Protective effect of GK2 fused BLVRA protein against oxidative stress‐induced dopaminergic neuronal cell damage

“…Thus PTDs have been applied as effective vehicles to deliver therapeutic molecules like protein, DNA, RNA, liposome and nanoparticles into cells because they have the ability to transduce into cells [21,22]. Among them, Tat-PTD derived from the human immunodeficiency virus is widely used to deliver the therapeutic protein into cells [23][24][25], and many groups have shown that Tat-fusion protein is transduced into a variety of cells, which were markedly protected against oxidative stress-induced cell death [26][27][28][29][30][31][32][33].…”