Critical Evaluation of the Changes in Glutamine Synthetase Activity in Models of Cerebral Stroke

Abstract

The following article addresses some seemingly paradoxical observations concerning cerebral glutamine synthetase in ischemia-reperfusion injury. In the brain, this enzyme is predominantly found in astrocytes and catalyzes part of the glutamine-glutamate cycle. Glutamine synthetase is also thought to be especially sensitive to inactivation by the oxygen- and nitrogen-centered radicals generated during strokes. Despite this apparent sensitivity, glutamine synthetase specific activity is elevated in the affected tissues during reperfusion. Given the central role of the glutamine-glutamate cycle in the brain, we sought to resolve these conflicting observations with the view of providing an alternative perspective for therapeutic intervention in stroke.

Inhibition of mitochondrial 2-oxoglutarate dehydrogenase impairs viability of cancer cells in a cell-specific metabolism-dependent manner

“…In contrast, under similar conditions, SP-treated neurons were characterized by primary accumulation of glutamate, with the glutamine increase following, but never exceeding that of glutamate (Figure 8 ). The difference was the most obvious at low (0.2 mM SP for 2 h, Figure 8A ) and high (2 mM SP for 5 h, Figure 8B ) exposures of neurons to SP, confirming recent data on the presence of glutamine synthase not only in astrocytes, where the major part of the brain enzyme is localized, but also in neurons [ 55 ]. It was therefore of interest to determine if glutamate would increase in SP-exposed neuroblastoma cell lines.…”

Minireview on Glutamine Synthetase Deficiency, an Ultra-Rare Inborn Error of Amino Acid Biosynthesis

“…GS function is also regulated by many other factors, including β-catenin activation [45,46], hormonal regulation [47,48,49,50,51], pH variation [9,52], oxidative stress [40,53], glucose deprivation [54], ischemia [55,56], or glutamine concentration in culture medium [57]; however, a detailed description is beyond the scope of this mini-review.…”

Neurovascular Unit as a Source of Ischemic Stroke Biomarkers—Limitations of Experimental Studies and Perspectives for Clinical Application

“…This glutamine (Gln) synthetizing astrocytic enzyme is responsible for maintaining of Glu/Gln balance in physiological conditions [162]. It is sensitive to free oxygen and nitrogen radicals that inactivate it when released during the early phase of ischemia [72,73]. However, GS activity is rapidly restored, especially after transient ischemia [73,74].…”

“…It is sensitive to free oxygen and nitrogen radicals that inactivate it when released during the early phase of ischemia [72,73]. However, GS activity is rapidly restored, especially after transient ischemia [73,74]. The GS immunoreactivity has been reported to be increased within 3 h of postischemic reperfusion [75].…”