Drug-tolerant persister cancer cells are vulnerable to GPX4 inhibition.

Acquired drug resistance prevents cancer therapies from achieving stable and complete responses. Emerging evidence implicates a key role for non-mutational drug resistance mechanisms underlying the survival of residual cancer 'persister' cells. The persister cell pool constitutes a reservoir from which drug-resistant tumours may emerge.

Inhibition of vesicular glutamate uptake by Rose Bengal-related compounds: structure-activity relationship.

Synaptic vesicular accumulation of glutamate is a vital initial step in glutamate transmission. We have previously shown that Rose Bengal, a polyhalogenated fluorescein analog, is a potent inhibitor of glutamate uptake into synaptic vesicles. Here, we report the structural features of Rose Bengal required for this inhibition.

Glycolysis and glutamate accumulation into synaptic vesicles. Role of glyceraldehyde phosphate dehydrogenase and 3-phosphoglycerate kinase.

Glucose is the major source of brain energy and is essential for maintaining normal brain and neuronal function. Hypoglycemia causes impaired synaptic transmission. This occurs even before significant reduction in global cellular ATP concentration, and relationships among glycolysis, ATP supply, and synaptic transmission are not well understood.

Prolonged depolarization of rat cerebral synaptosomes leads to an increase in vesicular glutamate content.

Glutamate accumulation into synaptic vesicles is a vital step in glutamate synaptic transmission. In this study, we have explored the possibility that vesicular glutamate storage may be subject to some regulation. Synaptosomes were depolarized and subjected to [3H] glutamate under non-depolarizing conditions, and vesicular [3H] glutamate content was determined by a filter-based assay.

Inhibition of vesicular glutamate storage and exocytotic release by Rose Bengal.

It had been thought that quantal size in synaptic transmission is invariable. Evidence has been emerging, however, that quantal size can be varied under certain conditions. We present evidence that alteration in vesicular [(3)H]L-glutamate (Glu) content within the synaptosome (a pinched-off nerve ending preparation) leads to a change in the amount of exocytotically released [(3)H]Glu.