Proliferation-dependent vulnerability of glucose-deprived astrocytes to nitric oxide-induced cytotoxicity

Mimosine prevents the death of glucose‐deprived immunostimulated astrocytes by scavenging peroxynitrite

“…Mimosine has been shown to inhibit the death of trophic factor-deprived PC 12 cells and sympathetic neurons (Farinelli and Greene, 1996;Park et al, 1997). Previously, we reported that immunostimulated astrocytes became highly susceptible to glucose deprivation and that this increased vulnerability depended on the proliferative state of the cells (Choi and Kim, 1998b). Thus, we hypothesized that mimosine might prevent the augmented astroglial death by inhibiting progression of the astrocytes through the cell cycle.…”

“…Previously, we reported that immunostimulated astrocytes are highly vulnerable to glucose deprivation (GD), a common occurrence in cerebral ischemia (Choi and Kim, 1998a,b). The increased death of glucosedeprived immunostimulated astrocytes occurred depending on their proliferative state (Choi and Kim, 1998b). This enhanced vulnerability was derived from the overexpression of inducible nitric oxide synthase (iNOS) and from the resultant increase of peroxynitrite level (Choi and Kim, 1998a,b).…”

Protection by a manganese porphyrin of endogenous peroxynitrite-induced death of glial cells via inhibition of mitochondrial transmembrane potential decrease

“…Glial cells were cultured from the prefrontal cortices of 2-to 5-day-old Sprague-Dawley rat pups as previously described (Choi and Kim, 1998a). In brief, cells were dissociated by mild trypsinization (10 min at 37°C with Dulbecco's modified Eagle medium [DMEM] containing 0.1% trypsin) and passed through sterile nylon sieves (80-m pore size) into DMEM containing 10% heat-inactivated fetal bovine serum (FBS).…”

Blockade of peroxynitrite-mediated astrocyte death by manganese(III)-cyclam

“…Astrocytes were cultured from the prefrontal cortices of 2-to 5-day-old SpragueÁ/Dawley rat pups as previously described (Choi and Kim, 1998). In our preliminary experiments, over 95% of the cells were immunoreactive for glial fibrillary acidic protein, an astrocyte-specific marker.…”

“…The cytotoxicity of NO is increased by reaction with superoxide anion (O 2 ( ) to form the highly reactive peroxynitrite (ONOO ( ) (Beckman et al, 1990). Previously, we reported that immunostimulated astrocytes became highly vulnerable to glucose deprivation (Choi and Kim, 1998;Choi et al, 2000Choi et al, , 2001. We found that the augmented death was caused by the collapse of antioxidant system (e.g., depletion of reduced glutathione) and resultant increase of peroxynitrite level in glucosedeprived immunostimulated astrocytes .…”