Abstract
Background Dynamin related protein-1 (Drp1)-mediated mitochondrial fission relates to ischemia reperfusion (IR) injury, and its association with necroptosis is implied. We hypothesized that receptor-interacting protein 1 (RIP1), a key kinase in necroptosis, acted as an upstream of Drp1-mediated mitochondrial fission during skeletal muscle IR. Methods Thirty rats were randomized into the SM, IR, NI, MI, and DI group (n = 6). The rats in the SM group were shamly operated, and those in the IR group were subjected to 4-hour ischemia of the right hindlimb that was followed by 4-hour reperfusion. Intraperitoneal administration of Nec-1 1 mg/kg, Mdivi-1 1.2 mg/kg and same volume of DMSO were given before ischemia in the NI, MI and DI groups, respectively. Upon reperfusion, the soleus muscles were harvested to determine morphological changes and the expression of RIP1, total Drp1 and p-Drp1 (Ser616). Moreover, the muscular oxidative stress indicators and plasma muscle damage biomarkers were detected. Results IR led to impaired histopathological structures and mitochondrial fragmentation in the soleus muscle tissue, accompanied with increased muscular oxidative stress and muscle injury biomarkers, which could be similarly alleviated by Mdivi-1 and Nec-1 (p < 0.05). RIP1 and p-Drp1 (Ser616) protein levels were significantly upregulated in the soleus muscle subjected to IR injury, this upregulation was attenuated in the NI group, and Mdivi-1 downregulated the protein expression of p-Drp1 (Ser616) but not of RIP1 (p < 0.05). Conclusion RIP1 functions as an upstream of Drp1-mediated mitochondrial fission in the execution of necroptosis during skeletal muscle IR.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.