Deletion of mammalian sterile 20-like kinase 1 attenuates neuronal loss and improves locomotor function in a mouse model of spinal cord trauma.

Abstract

Neuronal cell death following spinal cord injury (SCI) is an important contributor to neurological deficits. The purpose of our work was to delineate the function of mammalian sterile 20-like kinase 1 (Mst1), a pro-apoptotic kinase and key mediator of apoptotic signaling, in the pathogenesis of an experimental mouse model of SCI. Male mice received a mid-thoracic spinal contusion injury, and it was found that phosphorylation of Mst1 at the injured site was enhanced significantly following SCI. Furthermore, when compared to the wild-type controls, Mst1-deficient mice displayed improved locomotor function by increased Basso mouse scale score. Deletion of Mst1 in mice attenuated loss of motor neurons and suppressed microglial and glial activation following SCI. Deletion of Mst1 in mice reduced apoptosis via suppressing cytochrome c release and caspase-3 activation following SCI. Deletion of Mst1 attenuated mitochondrial dysfunction and increased ATP formation following SCI. Deletion of Mst1 in mice inhibited local inflammation following SCI, evidenced by reduced activities of myeloperoxidase and protein levels of TNF-α, IL-1β, and IL-6. In conclusion, the present study demonstrated that deletion of Mst1 attenuated neuronal loss and improved locomotor function in a mouse model of SCI, via preserving mitochondrial function, attenuating mitochondria-mediated apoptotic pathway, and suppressing inflammation, at least in part.

• Authors: Pan-Feng Wang, Da-Yuan Xu, Yuntong Zhang, Xiao-Bin Liu, Yan Xia, Pan-Yu Zhou, Qing-Ge Fu, Shuo-Gui Xu
• Journal: Molecular and cellular biochemistry (Mol Cell Biochem) Vol. 431 Issue 1-2 Pg. 11-20 (Jul 2017) ISSN: 1573-4919 [Electronic] Netherlands
• PMID: 28210902 (Publication Type: Journal Article)

Chemical References

• Cytokines
• Stk4 protein, mouse
• Protein Serine-Threonine Kinases
• Casp3 protein, mouse
• Caspase 3

Topics

• Animals
• Apoptosis
• Caspase 3 (genetics, metabolism)
• Cytokines (genetics, metabolism)
• Disease Models, Animal
• Gene Deletion
• Locomotion
• Mice
• Mice, Knockout
• Protein Serine-Threonine Kinases (deficiency, metabolism)
• Spinal Cord Injuries (enzymology, genetics, pathology, physiopathology)