Oncosis: An important non-apoptotic mode of cell death

Weerasinghe, Priya; Buja, L. Maximilian

doi:10.1016/j.yexmp.2012.09.018

Cited by 198 publications

(196 citation statements)

References 65 publications

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“…These characteristics of cell death induced by NADA are consistent with typical features of cell death termed oncosis (36,39,40). Like other cases of oncosis (41), cleavage of caspase-3 can be detected in NADA-treated Ba/F3-N cells (Supplementary Fig.…”

Section: Lead Compound Identificationsupporting

confidence: 82%

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N-Arachidonoyl Dopamine Inhibits NRAS Neoplastic Transformation by Suppressing Its Plasma Membrane Translocation

Huang

Zhang

et al. 2017

Molecular Cancer Therapeutics

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RAS oncogenic mutations are common in human cancers, but RAS proteins have been difficult to target. We sought to identify pharmacological agents to block RAS oncogenic signaling by a distinct mechanism. Because the biological activity of RAS proteins relies upon lipid modifications and RAS regulates lipid metabolisms in cancer cells, we screened a bioactive lipid library using a RAS-specific cell viability assay. We report the discovery of a new class of inhibitors for RAS transformation. Compounds in the class represented by endocannabinoid N-arachidonoyl dopamine (NADA) can induce cell oncosis, independent of its ability to engage cannabinoid receptors. Further analyses show that NADA is more active in inhibiting the NRAS transformation and signaling than that of KRAS4B. Mechanistically, NADA blocks the plasma membrane translocation of NRAS, but not that of KRAS4B. In addition, NADA inhibits plasma membrane translocation and neoplastic transformation of oncogenic KRAS4A. Interestingly, NADA also redistributes the cytoplasmic NRAS to the Golgi apparatus in a palmitoylation-dependent manner. The results indicate that NADA inhibits NRAS and KRAS4A plasma membrane translocation by targeting a novel molecular process. The new findings would help to develop novel targeted therapies for a broad range of human cancers.

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Section: Lead Compound Identificationsupporting

confidence: 82%

“…Oncotic cell death involves progressive membrane injury (39). It is possible that NADA affects transportation of molecules that regulate cell osmolarity.…”

Section: Discussionmentioning

confidence: 99%

N-Arachidonoyl Dopamine Inhibits NRAS Neoplastic Transformation by Suppressing Its Plasma Membrane Translocation

Huang

Zhang

et al. 2017

Molecular Cancer Therapeutics

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“…Thus, the mitochondria in young nr PNs share features of enlargement and rounding recognized in mitochondria engaged in mitoptosis (57,58) but differ in that few of the mitochondria develop fragmented cristae or other degenerative changes except at much older ages. The nr mitochondrial phenotype may signify the onset of PN death, but it does not fit easily into the current standard classification of celldeath types (59,60).…”

Section: Discussionmentioning

confidence: 99%

Tissue plasminogen activator regulates Purkinje neuron development and survival

Li¹,

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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The cerebellar cortex is centrally involved in motor coordination and learning, and its sole output is provided by Purkinje neurons (PNs). Growth of PN dendrites and their major synaptic input from granule cell parallel fiber axons takes place almost entirely in the first several postnatal weeks. PNs are more vulnerable to cell death than most other neurons, but the mechanisms remain unclear. We find that the homozygous nervous (nr) mutant mouse's 10-fold-increased cerebellar tissue plasminogen activator (tPA), a part of the tPA/plasmin proteolytic system, influences several different molecular mechanisms, each regulating a key aspect of postnatal PN development, followed by selective PN necrosis, as follows. (i) Excess endogenous or exogenous tPA inhibits dendritic growth in vivo and in vitro by activating protein kinase Cγ and phosphorylation of microtubule-associated protein 2. (ii) tPA/plasmin proteolysis impairs parallel fiber-PN synaptogenesis by blocking brain-derived neurotrophic factor/tyrosine kinase receptor B signaling. (iii) Voltage-dependent anion channel 1 (a mitochondrial and plasma membrane protein) bound with kringle 5 (a peptide derived from the excess plasminogen) promotes pathological enlargement and rounding of PN mitochondria, reduces mitochondrial membrane potential, and damages plasma membranes. These abnormalities culminate in young nr PN necrosis that can be mimicked in wild-type PNs by exogenous tPA injection into cerebellum or prevented by endogenous tPA deletion in nr:tPA-knockout double mutants. In sum, excess tPA/plasmin, through separate downstream molecular mechanisms, regulates postnatal PN dendritogenesis, synaptogenesis, mitochondrial structure and function, and selective PN viability. plasma membrane integrity | postnatal development | spinocerebellar ataxia | synaptic ultrastructure

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“…Наряду с апоптозом и некрозом выделяют ещё один тип клеточной смерти -онкоз [29][30]. Термин онкоз происходит от греческого слова, означающего "опухоль".…”

Section: происхождение цирднк в результате онкоза (рис 1г)unclassified

Generation of blood circulating DNA: the sources, peculiarities of circulation and structure

Bryzgunova

Laktionov

2015

BIOMED KHIM

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Внеклеточные нуклеиновые кислоты (внНК) в циркуляции как здоровых, так и больных людей были впервые описаны в 1948 г., однако оставались без внимания до середины 60-х годов прошлого века. внНК особенно интенсивно исследуются в последние 5 лет. Основное внимание уделяется исследованию внНК как источнику диагностического материала; однако механизмы генерации внеклеточных нуклеиновых кислот, а также механизмы, обеспечивающие их долговременную циркуляцию в кровотоке, однозначно не установлены. По данным одних авторов, основным источником циркулирующих дезоксирибонуклеиновых кислот в крови (цирДНК) являются процессы некроза и апоптоза, другие ссылаются на возможную секрецию нуклеиновых кислот как здоровыми, так и опухолевыми клетками. Известно, что цирДНК могут циркулировать в крови в течение длительного времени, ускользая от действия ДНК-гидролизующих ферментов крови и, по-видимому, находясь в составе надмолекулярных комплексов. В этом обзоре представлены данные разных авторов и приведены доказательства в пользу всех предложенных теорий появления цирДНК, описаны особенности строения цирДНК, а также факторы, влияющие на время циркуляции ДНК в крови.Ключевые слова: циркулирующая ДНК, апоптоз, некроз, активная секреция, ДНКазы, метилирование.

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Oncosis: An important non-apoptotic mode of cell death

Cited by 198 publications

References 65 publications

N-Arachidonoyl Dopamine Inhibits NRAS Neoplastic Transformation by Suppressing Its Plasma Membrane Translocation

N-Arachidonoyl Dopamine Inhibits NRAS Neoplastic Transformation by Suppressing Its Plasma Membrane Translocation

Tissue plasminogen activator regulates Purkinje neuron development and survival

Generation of blood circulating DNA: the sources, peculiarities of circulation and structure

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