Review articleRedox and oxidant-mediated regulation of apoptosis signaling pathways: immuno-pharmaco-redox conception of oxidative siege versus cell death commitment
Introduction
The regulation of programmed cell death, or apoptosis, can be considered as one mechanism, which is closely associated with cell development and another, which is involved in maintaining cell integrity and homeostasis. The asynchronous nature of cell death is attributed to variable duration and timing of events and the actual propagation of the apoptotic process. The multi-faceted complexity by which apoptosis is controlled requires the coordinated regulation of signaling cofactors, transcription factors and the presence of an extracellular motivation, which is represented by the effect of stimuli such as reactive oxygen and nitrogen species [1], [2], [3], [4], [5]. The airway epithelium has versatile roles that are key components of the mechanisms which help maintain and perpetuate the integrity and welfare of this delicate tissue of the lung. The integrity of the airway epithelium is particularly reinforced by a tightly regulated equilibrium existing between cell proliferation/differentiation and degeneration (apoptosis). This review summarizes our recent understanding of the mechanisms that regulate programmed cell death in physiologic and pathologic conditions, while focusing on elaborating pharmaco-redox concepts underlying pathways of redox/oxygen signaling mediating apoptosis.
Section snippets
Biochemical and biophysical properties that characterize the airway epithelium
Apoptosis, or programmed cell death (also referred to as an ‘orderly cell deletion’), is a genetically controlled mechanism involved in development, maturation and homeostasis [1], [2], [3], [4], [5]. The term ‘apoptosis’ is often used interchangeably with ‘programmed cell death’. In the strictest sense, programmed cell death may be applied to other forms of cell death that require gene expression without fulfilling some, or all, of the morphological criteria of apoptosis. Whatever the
Cell death regulation: the immunopharmacologic paradigm of necrosis versus apoptosis
In the last few decades, since the term ‘apoptosis’ was coined [33], [34], a vast quantity of work has been performed in search of the cause of the phenomenon it originally alluded to. It became clear, however, that some cells are genetically programmed, or destined, for death during the normal development of multi-cellular organisms [35]. The general apoptotic model today is one of intercellular signaling molecules operating in intracellular effector systems that balance each individual cell's
Redox dynamic equilibrium as determined by the glutathione/glutathione disulfide couple
‘Reduction-oxidation’ (redox) state is a term often widely adopted in the burgeoning field of free radical research and oxidative stress [29], [30], [43], [44]. The major determinant of redox status in mammalian cells is glutathione (GSH; l-γ-glutamyl-l-cysteinyl-glycine), a tripeptide thiol that couples with its disulfide form (GSSG) as a redox buffer system (2GSH/GSSG; GSSG+2H++2e−→2GSH) (Fig. 2) [45], [46]. According to Walter H. Nernst's theory, redox potential can be determined by the
Conclusions and future prospects
Apoptosis research continues apace—a burgeoning field with fascinating and promising outcomes through immunopharmacologic gene therapy and tissue modulation. Apoptosis is a complex and multi-faceted pre-programmed process that involves a plethora of signaling cofactors which span the cell membrane all the way down to the nucleus. Despite this diversity and complexity, apoptotic pathways ultimately converge to cause a process that may well be part of proliferation and differentiation—as in
Acknowledgements
This manuscript was written at UCSF, when the author was a postdoctoral fellow. The author appreciatively thanks Jennifer Schuyler (UCSF) for her excellent editing and reviewing of this manuscript. The author's own publications are financially supported by the Anonymous Trust (Scotland), the National Institute for Biological Standards and Control (England), the Tenovus Trust (Scotland), the UK Medical Research Council (MRC, London) and the Wellcome Trust (London). Dr. John J. Haddad held the
References (137)
- et al.
Programmed cell death: alive and well in the new millennium
Trends Cell Biol.
(2001) - et al.
Alveolar type II cell apoptosis
Comp. Biochem. Physiol.
(2001) - et al.
Signaling pathways and effector mechanisms pre-programmed cell death
Bioorg. Med. Chem.
(2001) - et al.
Apoptosis: definition, mechanisms, and relevance to disease
Am. J. Med.
(1999) - et al.
Therapeutic applications of apoptosis research
Exp. Cell Res.
(2000) - et al.
Regulation of redox glutathione levels and gene transcription in lung inflammation: therapeutic approaches
Free Radic. Biol. Med.
(2000) - et al.
Immunomodulatory potential of thymulin-Zn2+ in the alveolar epithelium: amelioration of endotoxin-induced cytokine release and partial amplification of a cytoprotective IL-10-sensitive pathway
Biochem. Biophys. Res. Commun.
(2000) - et al.
Chemioxyexcitation (ΔpO2/ROS)-dependent release of IL-1β, IL-6 and TNF-α: evidence of cytokines as oxygen sensitive mediators in the alveolar epithelium
Cytokine
(2001) - et al.
A non-hypoxic, ROS-sensitive pathway mediates TNF-α-dependent regulation of HIF-1α
FEBS Lett.
(2001) Oxidative stress and lung inflammation in airway disease
Eur. J. Pharmacol.
(2001)
Antioxidant/pro-oxidant equilibrium regulates HIF-1α and NF-κB redox sensitivity: evidence for inhibition by glutathione oxidation in alveolar epithelial cells
J. Biol. Chem.
Airway epithelium: more than just a barrier
Trends Pharmacol. Sci.
Deciphering the pathways of life and death
Curr. Opin. Cell Biol.
Redox-dependent signal transduction
FEBS Lett.
Redox environment of the cell as viewed through the redox state of the glutathione disulfide/glutathione couple
Free Radic. Biol. Med.
Glutathione and its role on cellular functions
Free Radic. Biol. Med.
Is oxidative stress central to the pathogenesis of chronic obstructive pulmonary disease?
Trends Mol. Med.
Systemic and pulmonary oxidative stress in idiopathic pulmonary fibrosis
Free Radic. Biol. Med.
Cellular oxygen toxicity
J. Biol. Chem.
Oxidant-mediated lung epithelial cell tolerance: The role of intracellular glutathione and nuclear factor-κB
Biochem. Pharmacol.
Hypothesis: the role of reactive sulfur species in oxidative stress
Free Radic. Biol. Med.
Oxidative stress and apoptosis
Pathophysiology
Oxidative stress as a mediator of apoptosis
Immunol. Today
Signal transduction mechanisms involving nitric oxide
Biochem. Pharmacol.
Induction of human neutrophil apoptosis by nitric oxide donors: evidence for a caspase-dependent, cyclic-GMP-independent, mechanism
Biochem. Pharmacol.
The regulatory role of nitric oxide in apoptosis
Int. Immunopharmacol.
Oxidative damage to mitochondria is a preliminary step to caspase-3 activation in fluoride-induced apoptosis in HL-60 cells
Free Radic. Biol. Med.
Cell death by reactive oxygen species generated from water-soluble cationic metalloporphyrins as superoxide dismutase mimics
J. Inorg. Biochem.
Antioxidants, programmed cell death, and cancer
Nutr. Res.
Signal transduction pathways in hyperoxia-induced lung cell death
Mol. Genet. Metab.
The differential expression of apoptosis factors in the alveolar epithelium is redox sensitive and requires NF-κB (RelA)-selective targeting
Biochem. Biophys. Res. Commun.
The ex vivo differential expression of apoptosis signaling cofactors in the developing lung: essential role of oxygenation during the transition from placental to pulmonary-based respiration
Biochem. Biophys. Res. Commun.
Redox signaling and transition metals in the control of the p53 pathway
Biochem. Pharmacol.
Hyperoxia inhibits oxidant-induced apoptosis in lung epithelial cells
J. Biol. Chem.
Apoptosis or necrosis: Intracellular levels of glutathione influence mode of cell death
Biochem. Pharmacol.
Glutathione levels determine apoptosis in macrophages
Biochem. Biophys. Res. Commun.
Airway epithelium and apoptosis
Apoptosis
Apoptosis signaling
Annu. Rev. Biochem.
Signaling apoptosis: a radical approach
Redox Rep.
P21Waf1/Cip1/Sdi1 and p53 expression in association with DNA strand breaks in idiopathic pulmonary fibrosis
Am. J. Respir. Crit. Care Med.
Is there any relationship between plasma antioxidant capacity and lung function in smokers and in patients with chronic obstructive pulmonary disease?
Thorax
Apoptosis and its clinical impact
Head Neck
Fas/FasL-dependent apoptosis of alveolar cells after lipopolysaccharide-induced lung injury in mice
Am. J. Respir. Crit. Care Med.
Oxidants and antioxidants as therapeutic targets in chronic obstructive pulmonary disease
Am. J. Respir. Crit. Care Med.
Dynamic changes in apoptotic and necrotic cell death correlate with severity of ischemia-reperfusion injury in lung transplantation
Am. J. Respir. Crit. Care Med.
Lung glutathione and oxidative stress: implications in cigarette smoke-induced airway disease
Am. J. Physiol., Lung Cell Mol. Physiol.
Apoptosis of airway epithelial cells induced by corticosteroids
Am. J. Respir. Crit. Care Med.
Cellular and molecular characteristics of basal cells in airway epithelium
Exp. Lung Res.
An electron microscope study of the fetal development of human lung
Pediatrics
The alveolar surface network: a new anatomy and its physiological significance
Anat. Rec.
Cited by (122)
Extraction of phenolic compounds
2023, Green Sustainable Process for Chemical and Environmental Engineering and Science: Green Solvents and Extraction TechnologyA review of pharmacological and pharmacokinetic properties of Forsythiaside A
2021, Pharmacological ResearchFerulic acid-mediated modulation of apoptotic signaling pathways in cancer
2021, Advances in Protein Chemistry and Structural BiologySenna plant generates reactive oxygen species (ROS) and induces apoptosis in Hymenolepis diminuta
2020, Molecular and Biochemical Parasitology