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Myocardial protective effects of a c-Jun N-terminal kinase inhibitor in rats with brain death
Wenzhi Guo1,2, Shengli Cao1,2, Bing Yan2
1Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Abstract:
To investigate whether the mitochondrial apoptotic pathway mediates myocardial cell injuries in rats under brain death (BD), and observe the effects and mechanisms of the c-Jun N-terminal kinase (JNK) inhibitor SP600125 on cell death in the heart. Forty healthy male Sprague-Dawley (SD) rats were randomized into four groups: sham group (dural external catheter with no BD); BD group (maintain the induced BD state for 6 hrs); BD + SP600125 group (intraperitoneal injection of SP600125 10 mg/kg 1 hr before inducing BD, and maintain BD for 6 hrs); and BD + Dimethyl Sulphoxide (DMSO) group (intraperitoneal injection of DMSO 1 hr before inducing BD, and maintain BD for 6 hrs). Real-time quantitative PCR was used to evaluate mRNA levels of Cyt-c and caspase-3. Western blot analysis was performed to examine the levels of mitochondrial apoptosis-related proteins p-JNK, Bcl-2, Bax, Cyt-c and Caspase-3. TUNEL assay was employed to evaluate myocardial apoptosis. Compared with the sham group, the BD group exhibited increased mitochondrial apoptosis-related gene expression, accompanied by the elevation of p-JNK expression and myocardial apoptosis. As the vehicle control, DMSO had no treatment effects. The BD + SP600125 group had decreased p-JNK expression, and reduced mitochondrial apoptosis-related gene expression. Furthermore, the apoptosis rate of myocardial cells was reduced. The JNK inhibitor SP600125 could protect myocardial cells under BD through the inhibition of mitochondrial apoptosis-related pathways.
Insights
Brain death (BD) induces myocardial cell injury via mitochondrial apoptosis. The c-Jun N-terminal kinase (JNK) inhibitor SP600125 protected heart cells by reducing apoptosis signaling.
Area of Science:
- Cardiology
- Molecular Biology
- Cell Death Research
Background:
- Brain death (BD) is a critical condition that can lead to systemic organ damage.
- Mitochondrial apoptotic pathways are implicated in myocardial cell injury.
- The role of c-Jun N-terminal kinase (JNK) in BD-induced cardiac apoptosis requires further elucidation.
Purpose of the Study:
- To investigate the involvement of the mitochondrial apoptotic pathway in myocardial cell injury during BD in rats.
- To evaluate the protective effects and underlying mechanisms of the JNK inhibitor SP600125 on cardiac cells under BD conditions.
Main Methods:
- Establishment of a rat model of brain death (BD).
- Treatment groups included sham, BD, BD + SP600125, and BD + DMSO (vehicle control).
- Analysis of apoptosis-related gene and protein expression (Cyt-c, caspase-3, p-JNK, Bcl-2, Bax) using RT-qPCR and Western blot.
- Assessment of myocardial apoptosis via TUNEL assay.
Main Results:
- BD significantly increased mitochondrial apoptosis-related gene expression, p-JNK levels, and myocardial apoptosis compared to the sham group.
- SP600125 treatment markedly reduced p-JNK expression and suppressed mitochondrial apoptosis-related gene expression.
- The apoptosis rate of myocardial cells was significantly decreased in the BD + SP600125 group compared to the BD group.
Conclusions:
- The mitochondrial apoptotic pathway mediates myocardial cell injuries in rats subjected to brain death.
- The JNK inhibitor SP600125 demonstrates a protective effect on myocardial cells during BD.
- SP600125 exerts its protective effects by inhibiting the mitochondrial apoptosis-related pathways, specifically through JNK signaling.
