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 1h 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.
Yao
Xiaomei
X
Department of Pathophysiology, Tianjin Medical University, Tianjin 300070, PR China. jupx@163.com
D000447:Aldehydes / Q000378:metabolism*; D000818:Animals; D002470:Cell Survival; D002478:Cells, Cultured; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism*; D051379:Mice; D009046:Motor Neurons / Q000737:chemistry / Q000187:drug effects*; D009457:Neuroglia / Q000737:chemistry* / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000032:analysis; D018091:Receptors, AMPA / Q000187:drug effects; D018092:Kainic Acid Receptors / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects*; D015032:Zinc / Q000633:toxicity*
D000447:Aldehydes; D027342:Excitatory Amino Acid Transporter 2; D017382:Reactive Oxygen Species; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D015032:Zinc; C027576:4-hydroxy-2-nonenal