Glutamate receptors modulate oxidative stress in neuronal cells. A mini-review

Abstract

Multiple lines of evidence demonstrate that reactive oxygen species (ROS) are involved in regulation of normal cell metabolism as second messengers. Under extreme conditions, these molecules induce oxidative stress, which may stimulate (or accompany) a number of neurodegenerative processes. In the glutamatergic system, ROS levels are under control of ionotropic and metabotropic glutamate receptors, which modulate ion fluxes through the neuronal membrane. The Na+/K(+)-pump is also one of the important participants affecting stationary ROS levels through several distinct mechanisms. This review describes the involvement of the Na+/K(+)-pump in intracellular signaling mechanisms via cross-talk between the pump and glutamate receptors in cerebellum granule cells. Selective dysfunction of mGlu II receptors may also lead to abnormal protein phosphorylation (i.e., tau phosphorylation), culminating in neurodegenerative disorders (i.e., Alzheimer disease). Also, unregulated production of intracellular ROS resulting from an imbalance of ionotropic and metabotropic receptors may activate one or more protein kinases. In summary, Glu receptor dysfunction, leading to a deficit in glutamate-mediated signal transduction may represent one of the earliest stages of neurodegenerative disorders. The Na+/K(+)-pump is able to prevent over-production of intracellular ROS, thus increasing oxidative stability of neuronal cells.

Using an advanced intercross line to identify quantitative trait loci controlling immune response during collagen-induced arthritis

“…Both Gprc2a-rs5 and Gprc2a-rs1 are calcium-sensing receptors belonging to the metabotropic glutamate family of G-protein-coupled receptors, 24 which control the level of ROS production. 25 We also observed the sex effect on ROS products. Males produce more ROS than females, suggesting that sex hormones play a role in ROS generation.…”

A Review of Glutamate Receptors I: Current Understanding of Their Biology

“…There are five main factors necessary for the transition of Glu and Asp from neurotransmitters to excitotoxins. These include inadequate neuronal ATP levels, inadequate neuronal levels of magnesium (Mg ++ ); high concentrations of inflammatory prostaglandins; excessive free radical formation 51,52 , and inadequate removal of synaptic Glu 53,54 .…”

Mechanisms of Ischemic Induced Neuronal Death and Ischemic Tolerance

“…In addition, Hcy has been shown to inhibit methyltransferases, to suppress DNA reparation and to facilitate apoptosis when accumulated inside the cells . Autooxidation of Hcy metabolites results in H 2 0 2 accumulation (Gortz et al, 2004;Boldyrev, 2005) and long term incubation of neurons with Hcy metabolites induces necrotic cell death (Zieminska et al, 2003;Boldyrev et al, 2004). Homocysteine has also been shown to be elevated in other disorders of the CNS, e.g.…”