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JIP1 Deficiency Protects Retinal Ganglion Cells From Apoptosis in a Rotenone-Induced Injury Model.

ABSTRACT: Retinal ganglion cells (RGCs) undergo apoptosis after injury. c-Jun N-terminal kinase (JNK)-interacting protein 1 (JIP1) is a scaffold protein that is relevant to JNK activation and a key molecule known to regulate neuronal apoptosis. However, the specific role of JIP1 in the apoptosis of RGCs is currently undefined. Here, we used JIP1 gene knockout (KO) mice to investigate the importance of JIP1-JNK signaling in the apoptosis of RGCs in a rotenone-induced injury model. In adult JIP1 KO mice, the number and electrophysiological functions of RGCs were not different from those of wild-type (WT) mice. Ablation of JIP1 attenuated the activation of JNK and the cleavage of caspase-3 in the retina after rotenone injury and contributed to a lower number of TUNEL-positive RGCs, a greater percentage of surviving RGCs, and a significant reduction in the electrophysiological functional loss of RGCs when compared to those in WT controls. We also found that JIP1 was located in the neurites of primary RGCs, but accumulated in soma in response to rotenone treatment. Moreover, the number of TUNEL-positive RGCs, the level of activation of JNK and the rate of cleavage of caspase-3 were reduced in primary JIP1-deficient RGCs after rotenone injury than in WT controls. Together, our results demonstrate that the JIP1-mediated activation of JNK contributes to the apoptosis of RGCs in a rotenone-induced injury model in vitro and in vivo, suggesting that JIP1 may be a potential therapeutic target for RGC degeneration.

SUBMITTER: Liu W

PROVIDER: S-EPMC6804425 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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JIP1 Deficiency Protects Retinal Ganglion Cells From Apoptosis in a Rotenone-Induced Injury Model.

Liu Wenyi W Li Xue X Chen Xi X Zhang Jieqiong J Luo Linlin L Hu Qiumei Q Zhou Jiaxing J Yan Jun J Lin Sen S Ye Jian J

Frontiers in cell and developmental biology 20191015

Retinal ganglion cells (RGCs) undergo apoptosis after injury. c-Jun N-terminal kinase (JNK)-interacting protein 1 (JIP1) is a scaffold protein that is relevant to JNK activation and a key molecule known to regulate neuronal apoptosis. However, the specific role of JIP1 in the apoptosis of RGCs is currently undefined. Here, we used JIP1 gene knockout (KO) mice to investigate the importance of JIP1-JNK signaling in the apoptosis of RGCs in a rotenone-induced injury model. In adult JIP1 KO mice, th ...[more]

PMID: 31681759

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Project description:Background: Low-intensity pulsed ultrasound (LIPUS) has been used in clinical studies. But little is known about its effects on the central nervous system (CNS), or its mechanism of action. Retinal ganglion cells (RGCs) are CNS neuronal cells that can be utilized as a classic model system to evaluate outcomes of LIPUS protection from external trauma-induced retinal injury. In this study, we aim to: (1) determine the pulse energy and the capability of LIPUS in RGC viability, (2) ascertain the protective role of LIPUS in optic nerve (ON) crush-induced retinal injury, and 3) explore the cellular mechanisms of RGC apoptosis prevention by LIPUS. Methods: An ON crush model was set up to induce RGC death. LIPUS was used to treat mice eyes daily, and the retina samples were dissected for immunostaining and Western blot. The expression of yes-associated protein (YAP) and apoptosis-related proteins was detected by immunostaining and Western blot in vitro and in vivo. Apoptosis of RGCs was evaluated by TUNEL staining, the survival of RGCs and retained axons were labeled by Fluoro-gold and Tuj1 antibody, respectively. Rotenone was used to set up an in vitro cellular degenerative model and siYAP was used to interfering the expression of YAP to detect the LIPUS protective function. Results: LIPUS protected RGC from loss and apoptosis in vivo and in vitro. The ratio of cleaved/pro-caspase3 also decreased significantly under LIPUS treatment. As a cellular mechanical sensor, YAP expression increased and YAP translocated to nucleus in LIPUS stimulation group, however, phospho-YAP was found to be decreased. When YAP was inhibited, the LIPUS could not protect RGC from caspase3-dependent apoptosis. Conclusion: LIPUS prevented RGCs from apoptosis in an ON crush model and in vitro cellular degenerative model, which indicates a potential treatment for further traumatic ON injury. The mechanism of protection is dependent on YAP activation and correlated with caspase-3 signaling.

Dataset Information

JIP1 Deficiency Protects Retinal Ganglion Cells From Apoptosis in a Rotenone-Induced Injury Model.

Publications

JIP1 Deficiency Protects Retinal Ganglion Cells From Apoptosis in a Rotenone-Induced Injury Model.

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