Aims
During early development, laminin degradation contributes to the death of neurons. This study aims to investigate the role and regulation of laminin in ketamine-induced apoptosis.
Conclusion
Laminin degradation by MMP9 promoted ketamine-induced neuronal apoptosis in early developing rat retina. The non-integrin laminin receptor may be a pathway involved in ketamine-induced apoptosis. Zn2+ downregulation may play a protective role against ketamine-induced neuronal apoptosis through inhibiting MMP9 activity.
Methods
We performed terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) and immunohistochemical assays to investigate the roles of the non-integrin laminin receptor, matrix metalloproteinase 9 (MMP9) in ketamine-induced neuronal apoptosis. In situ zymography, Western blot, and immunofluorescence were used to explore the relationships between laminin, MMP9 activity, and Zn2+ . Experiments were performed using whole-mount retinas dissected from Sprague Dawley rats.
Results
The TUNEL and immunohistochemical assays indicated that ketamine-induced neuronal apoptosis in early developing rat retina. Blockade of non-integrin laminin receptor promoted ketamine-induced apoptosis, while non-integrin laminin receptor activation attenuated ketamine-induced apoptosis. Ketamine-induced laminin degradation, possibly by enhancing the activity of MMP9. MMP9 inhibition reduced ketamine-induced apoptosis by reducing laminin degradation. Downregulation of Zn2+ attenuated the increased MMP9 activity, laminin degradation caused by ketamine and significantly reduced ketamine-induced neuronal apoptosis.