Effect of zinc exposure on HNE and GLT-1 in spinal cord culture

Zinc has been closely linked to toxic injury in stroke; changes of 4-hydroxynonenal (HNE) and glutamate transporter (GLT-1) are implicated in cell death in amyotrophic lateral sclerosis (ALS). However, the effect of zinc exposure on the expression of HNE and GLT-1, and the survival of spinal cord motor neuron remains unknown. Here we demonstrate that under the activation of Ca2+ permeable AMPA/kainate (Ca-A/K) channels, zinc exposure for 1 h significantly increases the expression of HNE, decreases the expression of GLT-1 by immunostaining and Western blot, induces strong increase in reactive oxygen species (ROS) generation in Ca-A/K (+) neurons by hydroethidine (HEt) imaging and cobalt staining, and decreases the motor neuron survival in spinal cord culture. Interestingly, GLT-1 positive granules appear within the soma of glial cells 1 h after zinc exposure, while these granules are absent in the untreated control group. The increase of HNE and decrease of GLT-1 production caused by prolonged kainate stimulated zinc exposure may play a key role in oxidative neurotoxicity in spinal cord motor neurons, and may be relevant to chronic neurodegeneration.