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Updated: Dec 12, 2025
Evaluating Cell Death Signaling by Immunofluorescence in a Rat Model of Ischemic Stroke
Published on: January 3, 2025
ClC-3 induction protects against cerebral ischemia/reperfusion injury through promoting Beclin1/Vps34-mediated
Beilin Zhang1, Fang Deng1, Chunkui Zhou1
1Department of Neurology, The First Teaching Hospital of Jilin University, No. 71 Xinmin Street, Chaoyang District, Changchun, 130021, Jilin Province, People's Republic of China.
Abstract:
Acute ischemic stroke is a devastating disease with very limited therapeutics. Growing appreciation of dysregulated autophagy contributes to the progression of brain ischemic injury, making it to be an appealing intervention target. In terms of its well-characterized consequences, the signal molecules required for autophagy activation are rather poorly defined. Here, we found the induction of chloride channel-3 (ClC-3) directly activated autophagy, which played an important role in limiting cerebral ischemia/reperfusion (I/R) injury. Further mechanism exploration discovered that the up-regulation of ClC-3 was critical for the interaction of Beclin1 and Vps34. After ClC-3 knockdown using adeno-associated virus vectors in vivo, the autophagy activation was partially inhibited through disrupting the formation of Beclin1 and Vps34 complex. Consistent with these observations, ClC-3 knockdown could also significantly aggravated cerebral I/R injury through suppressing autophagy in vivo, which further confirmed the neuroprotective roles of ClC-3. Collectively, we provided an novel evidence for ClC-3 serving as a crucial regulator of autophagy; and our results indicated that the induction of ClC-3 may serve as a self-protective mechanism against cerebral I/R injury.
Insights
Chloride channel-3 (ClC-3) directly activates autophagy, a key process in limiting brain damage after ischemic stroke. Upregulating ClC-3 may be a self-protective mechanism against cerebral injury.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- Acute ischemic stroke causes significant brain injury with limited treatment options.
- Dysregulated autophagy is implicated in brain ischemic injury, presenting a therapeutic target.
- The specific signaling molecules that activate autophagy in this context are not well-defined.
Purpose of the Study:
- To investigate the role of chloride channel-3 (ClC-3) in regulating autophagy during cerebral ischemia/reperfusion (I/R) injury.
- To elucidate the molecular mechanisms by which ClC-3 influences autophagy.
- To determine the neuroprotective potential of ClC-3 induction in cerebral I/R injury.
Main Methods:
- Investigated the effect of ClC-3 induction on autophagy activation in a model of cerebral I/R injury.
- Explored the molecular interaction between ClC-3, Beclin1, and Vps34.
- Utilized adeno-associated virus vectors for in vivo ClC-3 knockdown to assess its impact on autophagy and injury.
Main Results:
- Chloride channel-3 (ClC-3) induction was found to directly activate autophagy.
- Upregulation of ClC-3 was essential for the interaction between Beclin1 and Vps34, crucial for autophagy.
- ClC-3 knockdown inhibited autophagy and exacerbated cerebral I/R injury, confirming its neuroprotective role.
Conclusions:
- ClC-3 acts as a critical regulator of autophagy.
- The Beclin1-Vps34 complex formation is modulated by ClC-3.
- Induction of ClC-3 represents a potential endogenous protective mechanism against cerebral I/R injury.
