Cytotoxic activity of acetylcholine receptor ligands

Blishchenko, Elena Yu.; Mirkina, Irina; Mernenko, Olga A.; Yatskin, Oleg N.; Satpaev, Daulet K.; Strizhkov, Boris N.; Karelin, A. A.

doi:10.1080/15216549700203171

Cited by 3 publications

(6 citation statements)

References 15 publications

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“…Just as with c-fos itself (45)(46)(47), the developmental context in which nicotine exposure occurs is likely to be critical for determining whether apoptosis is evoked or suppressed. Indeed, cholinergic agonists and antagonists can both elicit apoptosis depending on whether the context involves active or desensitized receptors (48). In the context of extended exposure to nicotine during fetal development, persistent induction of c-fos clearly is associated with enhanced cell death (31), most likely from apoptosis (40).…”

Section: Nicotine: Prototypic Cholinotoxicantmentioning

confidence: 99%

Developmental cholinotoxicants: nicotine and chlorpyrifos.

Slotkin

1999

Environ Health Perspect

244

167

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The stimulation of cholinergic receptors in target cells during a critical developmental period provides signals that influence cell replication and differentiation. Accordingly, environmental agents that promote cholinergic activity evoke neurodevelopmental damage because of the inappropriate timing or intensity of stimulation. Nicotine evokes mitotic arrest in brain cells possessing high concentrations of nicotinic cholinergic receptors. In addition, the cholinergic overstimulation programs the expression of genes that evoke apoptosis and delayed cell loss. Effects of cholinesterase inhibitors exhibit many similarities to those of nicotine. Chlorpyrifos administered to developing rats in doses that do not evoke signs of overt toxicity decreased DNA synthesis and caused shortfalls in cell numbers in brain regions enriched in cholinergic innervation. In embryo cultures, chlorpyrifos also evoked apoptosis during neurulation. However, chlorpyrifos also evokes noncholinergic disruption of cell development by interfering with cell signaling via adenylyl cyclase, leading to widespread disruption that is not limited to cholinergic systems. We have tested this hypothesis in vitro with PC12 cells, which lack the enzymes necessary to produce chlorpyrifos oxon, the metabolite that inhibits cholinesterase. Chlorpyrifos inhibited DNA synthesis in undifferentiated PC12 cells, which have relatively few cholinergic receptors. Furthermore, chlorpyrifos was more effective than nicotine and its effects were not blocked by cholinergic antagonists. When cells were allowed to differentiate in the presence of chlorpyrifos, cell replication was inhibited even more profoundly and cell acquisition was arrested. At higher concentrations, chlorpyrifos also inhibited neuritic outgrowth. Thus, chlorpyrifos elicits damage by both noncholinergic and cholinergic mechanisms extending from early stages of neural cell replication through late stages of axonogenesis and terminal differentiation. Accordingly, the window of developmental vulnerability to chlorpyrifos is likely to extend from the embryonic period into postnatal life. -Environ Health Perspect 107(Suppl 1): 71-80 (1999). http.//ehpnetl.niehs.nih.gov/docs/1999/Suppl-1/71-80slotkin/abstract.html

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Section: Nicotine: Prototypic Cholinotoxicantmentioning

confidence: 99%

Developmental cholinotoxicants: nicotine and chlorpyrifos.

Slotkin

1999

Environ Health Perspect

244

167

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“…First, the observed phenomenon is not re,~tricted to Met-enkephalin. Similar effects were also exerted b.x acetylcholine receptor antagonists: neurotoxin II [9], tuboctrarin [4] and some endogenous cytolytically active subst, races, including TNF and substance P [10].…”

Section: Resultsmentioning

confidence: 72%

Met‐enkephalin induces cytolytic processes of apoptotic type in K562 human erythroid leukemia cells

et al. 1996

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Cytolytic activity of Met-enke]~halin, an endogenous --17 opioid peptide, was studied within the 10--10 M concentration range in K562 human erythroid leukemia cells. Cytolytic activity was determined by the trypan blue inclusion method after 13, 15 and 18 h of Met-enkephalin co-incubation with target cells. Discrete maxima of cytolytic activity were detected at concentrations of 10-9-10 -1°, 10 -13 and 10 -aS M. Cytolysis was accompanied by internucleosomal DNA fragmentation which is indicative of the mechanism of cell death being apoptosis.

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“…tinued in publications of Piot et al reviewed in this issue of Peptide Science. 8 Moreover, hemorphinNeokyotorphin was shown to terminate the hibernation state in ground squirrels and to enhance the containing peptides were found in vivo in several 13 In contrast to neokyotorphin, the shortened by one C-terminal amino acid…”

Section: Peptides From Tissue Extractsmentioning

confidence: 98%

“…For instance, the level of neokyotorphin in rat lung is 4-5 times higher than in erythrocytes. 13 We believe that peptides released from the With more that 150 established amino acid sequences of endogenous hemoglobin fragments erythrocytes either accumulate in the tissue surrounding the blood vessel or are further degraded available for comparison, it is tempting to analyze the pathways of hemoglobin proteolysis in more by tissue-specific proteases. The observed level of peptides in the tissue extract is a sum of the contridetail.…”

Section: Proteolytic Degradation Of Hemoglobinmentioning

confidence: 99%

“…In principle, the globin tioned transformed cell lines. 13 genes can be expressed not only in red blood cells Peptides belonging to the hemorphin family [i.e., and therefore respective peptides might form diwith sequences spanning the b-globin (32-41) serectly within any cell. 46 However, the huge amount quence] were amply represented in the bovine brain of hemoglobin circulating inside the erythrocytes extracts (Table VII).…”

Section: Peptides From Tissue Extractsmentioning

confidence: 99%

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