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Updated: Jul 29, 2025
2-Vessel Occlusion/Hypotension: A Rat Model of Global Brain Ischemia
Published on: June 22, 2013
Tat-RAN attenuates brain ischemic injury in hippocampal HT-22 cells and ischemia animal model
Eun Ji Yeo1, Min Jea Shin1, Gi Soo Youn1
1Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, 24252, South Korea.
Abstract:
Oxidative stress plays a key role in the pathogenesis of neuronal injury, including ischemia. Ras-related nuclear protein (RAN), a member of the Ras superfamily, involves in a variety of biological roles, such as cell division, proliferation, and signal transduction. Although RAN reveals antioxidant effect, its precise neuroprotective mechanisms are still unclear. Therefore, we investigated the effects of RAN on HT-22 cell which were exposed to H2O2-induced oxidative stress and ischemia animal model by using the cell permeable Tat-RAN fusion protein. We showed that Tat-RAN transduced into HT-22 cells, and markedly inhibited cell death, DNA fragmentation, and reactive oxygen species (ROS) generation under oxidative stress. This fusion protein also controlled cellular signaling pathways, including mitogen-activated protein kinases (MAPKs), NF-κB, and apoptosis (Caspase-3, p53, Bax and Bcl-2). In the cerebral forebrain ischemia animal model, Tat-RAN significantly inhibited both neuronal cell death, and astrocyte and microglia activation. These results indicate that RAN significantly protects against hippocampal neuronal cell death, suggesting Tat-RAN will help to develop the therapies for neuronal brain diseases including ischemic injury.
Insights
Ras-related nuclear protein (RAN) fusion protein protects against oxidative stress and neuronal injury. Tat-RAN reduced cell death and inflammation in both cell cultures and an ischemia animal model, suggesting therapeutic potential for brain diseases.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Oxidative stress is a key factor in neuronal injury, particularly during ischemia.
- Ras-related nuclear protein (RAN) has known antioxidant effects, but its neuroprotective mechanisms are not fully understood.
Purpose of the Study:
- To investigate the neuroprotective effects of RAN using a cell-permeable Tat-RAN fusion protein.
- To elucidate the mechanisms underlying RAN's protection against oxidative stress and ischemia in neuronal cells.
Main Methods:
- Utilized HT-22 cells exposed to hydrogen peroxide (H2O2)-induced oxidative stress.
- Employed a cerebral forebrain ischemia animal model.
- Administered cell-permeable Tat-RAN fusion protein.
Main Results:
- Tat-RAN effectively transduced into HT-22 cells, significantly inhibiting cell death, DNA fragmentation, and reactive oxygen species (ROS) generation.
- Tat-RAN modulated key cellular signaling pathways, including mitogen-activated protein kinases (MAPKs), NF-κB, and apoptosis-related proteins (Caspase-3, p53, Bax, Bcl-2).
- In vivo, Tat-RAN significantly reduced neuronal cell death and suppressed astrocyte and microglia activation in a cerebral forebrain ischemia model.
Conclusions:
- RAN demonstrates significant neuroprotective effects against oxidative stress and ischemic injury.
- The Tat-RAN fusion protein shows promise as a therapeutic agent for neuronal brain diseases, including ischemic brain injury.
