Aging-US: PTEN nuclear translocation enhances neuronal injury after hypoxia-ischemia07-25-2021
Aging-US published "PTEN nuclear translocation enhances neuronal injury after hypoxia-ischemia via modulation of the nuclear factor-κB signaling pathway" which reported that this study was designed to investigate phosphatase and tensin homolog nuclear translocation and its possible role in rat cortical neuronal damage following oxygen-glucose deprivation in vitro.
In addition, PTEN expression was increased and the phosphorylation of extracellular signal-regulated kinase 1/2 and activation of nuclear factor kappa B were decreased following OGD.
PTENK13R transfection prevented PTEN nuclear translocation; attenuated the effect of OGD on nuclear p-ERK1/2 and NF-κB, apoptosis, and LDH release; and increased the expression of several anti-apoptotic proteins.
They conclude that PTEN nuclear translocation plays an essential role in neuronal injury following OGD via modulation of the p-ERK1/2 and NF-κB pathways.
Prevention of PTEN nuclear translocation might be a candidate strategy for preventing brain injury following HI.
Dr. Jing Zhao from The Affiliated Hospital of North Sichuan Medical College said, "Hypoxia-ischemia (HI) during fetal and neonatal development can cause damage to neurons, leading to neurological defects and even death."
PTEN possesses both protein phosphatase and lipid phosphatase activity and PTEN nuclear translocation induced by PTEN phosphatase activity has been linked to DNA damage in cancer cells.
Additionally, PTEN has been reported to localize to both the cytoplasm and nucleus of neurons, and an imbalance in its nucleocytoplasmic distribution has been linked to neuronal injury following excitotoxicity or ischemia.
These author’s previous studies showed that the inhibition of PTEN prevents neuronal injury after HI by mediating the activity of glycogen synthase kinase 3β and AKT.
However, the roles of PTEN in the regulation of ERK phosphorylation and NF-κB activity and their effects on the underlying mechanisms of neuronal injury remain unclear.
Figure 6. Inhibition of PTEN nuclear translocation reduces neural injury after OGD. (A) TUNEL-positive cells increased after OGD. This enhanced apoptosis was blocked in GFP-PTENK13R neurons. Scale bars = 50 μm. (B) Extracellular levels of LDH decreased in GFP-PTENK13R neurons after OGD. (C) Bcl-2 and Bcl-xL protein expression was evaluated by western blot which showed that their expression increased in GFP-PTENK13R neurons after OGD. (D) Quantification of Bcl-2 and Bcl-xL protein expression normalized against GFP-PTENWT neurons. n = 5 in each column and ** p < 0.01 vs. WT. ##p < 0.01, vs. WT. OGD: oxygen and glucose deprivation, GFP: green fluorescent protein, TUNEL: terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling WT: GFP-PTENWT neurons, K13R: GFP-PTENK13R neurons; P: PDTC.
They anticipate that this study could provide new perspectives into their understanding of the role of PTEN in neuronal injury and therapy development.
The Zhao Research Team concluded in their Aging-US Research Output, "our study provides insight into the molecular mechanisms through which PTEN nuclear translocation contributes to neuronal injury following HI. We found that PTEN nuclear translocation is an essential step in the activation of ERK1/2 and NF-κB in neurons subjected to OGD and that inhibition of PTEN nuclear translocation can provide protection against ischemic brain damage. PTENK13R mutants transfected into neurons effectively inhibited PTEN nuclear translocation, without affecting the cytoplasmic functions of PTEN. Taken together, these results suggest that the inhibition of PTEN nuclear translocation could be a potent novel strategy for protecting neurons following HI in vivo."
Full Text - https://www.aging-us.com/article/203141/text
Correspondence to: Jing Zhao email: Jenny_ZJ@yeah.net
Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research as well as topics beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, cancer, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR among others), and approaches to modulating these signaling pathways.