Krebs Cycle Intermediates Protective against Oxidative Stress by Modulating the Level of Reactive Oxygen Species in Neuronal HT22 Cells.

Krebs cycle intermediates (KCIs) are reported to function as energy substrates in mitochondria and to exert antioxidants effects on the brain. The present study was designed to identify which KCIs are effective neuroprotective compounds against oxidative stress in neuronal cells. Here we found that pyruvate, oxaloacetate, and α-ketoglutarate, but not lactate, citrate, iso-citrate, succinate, fumarate, or malate, protected HT22 cells against hydrogen peroxide-mediated toxicity. These three intermediates reduced the production of hydrogen peroxide-activated reactive oxygen species, measured in terms of 2',7'-dichlorofluorescein diacetate fluorescence. In contrast, none of the KCIs-used at 1 mM-protected against cell death induced by high concentrations of glutamate-another type of oxidative stress-induced neuronal cell death. Because these protective KCIs did not have any toxic effects (at least up to 10 mM), they have potential use for therapeutic intervention against chronic neurodegenerative diseases.

A novel, antimicrobially active analog of gramicidin S without amphiphilic conformation.

A novel gramicidin S analog, cyclo(-Val-Leu-Leu-Orn-Leu-D-Phe-Pro-)2, was synthesized, its antibiotic activity compared with gramicidin S and shown to be as potent as gramicidin S when compared with the susceptibility toward five Gram-positive microorganisms. It exceeded the activity of gramicidin S against Bacillus megaterium ATCC 19213 by a factor of two. Circular dichroism and NMR data suggested this analog to adopt an antiparallel beta-sheet conformation without amphiphilic character.