Life and death decisions

Ceramide generation and EGF receptor trafficking are modulated by oxidative stress

Tzipora Goldkorn, Tommer Ravid, Elaine M. Khan

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Reactive oxidants are associated with the pathogenesis of pulmonary diseases and affect various cell functions, from proliferation to apoptosis. We have shown that oxidants exert growth control on airway epithelial cells by modulating upstream receptor function. Additionally, hydrogen peroxide-mediated oxidative stress modulates ceramide levels to induce apoptosis in lung epithelium. Depletion of glutathione in lung epithelial cells results in ceramide accumulation, suggesting that ceramide elevation, coupled to oxidative stress, initiates apoptosis. While it is desirable to prevent cell death and tissue injury induced by oxidants in diseases such as asthma or acute respiratory distress syndrome, the opposite is sought in cancer. But oxidants may also activate growth factor receptors, enhancing cell proliferation and facilitating tumor promotion. Under oxidative stress, phosphorylation of the epidermal growth factor receptor (EGFR) is abrogated at tyrosine 1,045, the docking site for the ubiquitin ligase c-Cbl, rendering EGFR unable to recruit c-Cbl and be ubiquitylated and degraded. We thus proposed that this deficiency, which confers prolonged receptor signaling at the plasma membrane, links oxidative stress, EGFR, and tumorigenesis. Decoding the molecular interactions between oxidative stress and ceramide pathways and characterizing ubiquitylation control of receptor desensitization should provide new strategies for intervention in diverse pulmonary diseases and in diagnosing and eradicating cancer.

Original languageEnglish (US)
Pages (from-to)119-128
Number of pages10
JournalAntioxidants and Redox Signaling
Volume7
Issue number1-2
DOIs
StatePublished - Jan 2005

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Oxidative stress
Ceramides
Epidermal Growth Factor Receptor
Oxidative Stress
Oxidants
Pulmonary diseases
Apoptosis
Lung Diseases
Epithelial Cells
Cell Proliferation
Neoplasms
Lung
Phosphorylation
Airway Management
Growth Factor Receptors
Molecular interactions
Ubiquitination
Adult Respiratory Distress Syndrome
Cell proliferation
Cell death

ASJC Scopus subject areas

  • Biochemistry

Cite this

Life and death decisions : Ceramide generation and EGF receptor trafficking are modulated by oxidative stress. / Goldkorn, Tzipora; Ravid, Tommer; Khan, Elaine M.

In: Antioxidants and Redox Signaling, Vol. 7, No. 1-2, 01.2005, p. 119-128.

Research output: Contribution to journalArticle

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