Cyanide‐induced alteration of the adenylate energy pool in a rat neurosecretory cell line

Abstract

Cultures of a rat PC12 pheochromocytoma neurosecretory cell line were used to determine the responsiveness of oxidative energy status of isolated neuronal cells to cyanide exposure. Intracellular levels of ATP and its immediate metabolites, ADP and AMP, were measured in monolayer cultures of PC12 cells incubated for 0-30 min with KCN (10 mM). Over the period 2.5-30 min. cyanide treatment decreased ATP levels by 32-51% but ADP and AMP levels were not altered significantly. Additionally, ATP/ADP and ATP/AMP ratios were significantly reduced in KCN-intoxicated cells. These alterations in energy status may explain the prompt ablation of ion homeostasis reported previously in this model upon exposure to KCN. The energy-depleting actions of cyanide were not modified by pretreatment of cells with diltiazem, a calcium channel antagonist demonstrated to possess cytoprotective activity against histotoxic hypoxia induced by cyanide. Since PC12 cells rapidly respond to cyanide, with predictable depletions of the cell adenylate energy pool, this cell line can serve as a suitable in vitro model for studies of neurotoxicity involving ischemic/hypoxic conditions.

Identification of Cigarette Smoke Components That Alter Functioning of Hamster (Mesocricetus auratus) Oviducts In Vitro1

“…It is more probable that cyanide was acting by another mechanism. In addition, the concentration of KCN (10 mM) usually used to deplete ATP in flagellated or ciliated cells [27,28] is 200 times higher than the concentration of KCN (50 IM) that inhibited CBF and 666 times higher than the concentration (15 VIM) that inhibited OPR. These numbers indicate that proper functioning of the oviductal epithelium is sensitive to very low levels of cyanide, which appears to act by a mechanism other than ATP depletion.…”

“…Our study also shows that both CBF and OPR are highly sensitive to cyanide. The cyanide concentrations that inhibit CBF (50 txM) and OPR (15 AiM) are 200 and 666 times lower, respectively, than the concentration (10 mM) normally used to inhibit ATP production [27,28].…”

HIF-1α activation by a redox-sensitive pathway mediates cyanide-induced BNIP3 upregulation and mitochondrial-dependent cell death

“…At the cellular level, cyanide produces chemical hypoxia (histotoxic anoxia) by inhibiting cytochrome c oxidase in complex IV of the mitochondrial oxidative phosphorylation chain to markedly reduce ATP [1,2]. In neurons, cyanide increases cytosolic-free Ca 2+ by stimulating Ca 2+ influx, accompanied by rapid surge of ROS generation at complex I and III [3,4]. The mitochondrial dysfunction and ionic imbalance activates the cell death cascades in which apoptotic death occurs in cortical cells and necrosis in mesencephalic cells [5][6][7].…”

Successful use of a plant gene in the treatment of cancer in vivo

“…The glioblastoma tumor cell lines (C6, L9 or U373 MG), as well as one glioblastoma explant from a human patient, were 10 to 500 times more resistant to the toxic effect of exogenous sodium cyanide than ⌿CRIP cells. This finding could be related to the observation that malignant tumor cells (C6) have a low oxidative respiration rate and a decreased number of mitochondria, making them more resistant to metabolic poisons, such as KCN, 14,15 a property that can be partly reversed in vivo by the low pH conditions maintained within the tumor. Neoplastic cells forming a tumor are exposed to a substantial and consistent decrease in extracellular pH from 7.4 to 6.6 in the case of glioblastoma, or lower for other types of tumors 16,17 resulting in higher sensitivity (50% or greater) to the inhibitory effects of sodium cyanide.…”