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Updated: Jul 18, 2026
Analysis of Oxidative Stress in Zebrafish Embryos
Published on: July 7, 2014
Mechanisms of cell death in oxidative stress
Stefan W Ryter1, Hong Pyo Kim, Alexander Hoetzel
1Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, The University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA. Ryters@upmc.edu
Abstract:
Reactive oxygen or nitrogen species (ROS/RNS) generated endogenously or in response to environmental stress have long been implicated in tissue injury in the context of a variety of disease states. ROS/RNS can cause cell death by nonphysiological (necrotic) or regulated pathways (apoptotic). The mechanisms by which ROS/RNS cause or regulate apoptosis typically include receptor activation, caspase activation, Bcl-2 family proteins, and mitochondrial dysfunction. Various protein kinase activities, including mitogen-activated protein kinases, protein kinases-B/C, inhibitor-of-I-kappaB kinases, and their corresponding phosphatases modulate the apoptotic program depending on cellular context. Recently, lipid-derived mediators have emerged as potential intermediates in the apoptosis pathway triggered by oxidants. Cell death mechanisms have been studied across a broad spectrum of models of oxidative stress, including H2O2, nitric oxide and derivatives, endotoxin-induced inflammation, photodynamic therapy, ultraviolet-A and ionizing radiations, and cigarette smoke. Additionally ROS generated in the lung and other organs as the result of high oxygen therapy or ischemia/reperfusion can stimulate cell death pathways associated with tissue damage. Cells have evolved numerous survival pathways to counter proapoptotic stimuli, which include activation of stress-related protein responses. Among these, the heme oxygenase-1/carbon monoxide system has emerged as a major intracellular antiapoptotic mechanism.
Insights
Reactive oxygen and nitrogen species (ROS/RNS) contribute to cell death via apoptosis and necrosis, impacting various diseases. The heme oxygenase-1/carbon monoxide system acts as a key survival mechanism against oxidative stress.
Area of Science:
- Biochemistry
- Cell Biology
- Pathology
Background:
- Reactive oxygen and nitrogen species (ROS/RNS) are implicated in tissue injury and cell death pathways (apoptosis, necrosis) across diverse disease states.
- Oxidative stress, induced by various agents like H2O2, radiation, and cigarette smoke, triggers cellular damage.
- Cells possess survival mechanisms, including stress-related protein responses, to counteract pro-apoptotic stimuli.
Purpose of the Study:
- To elucidate the mechanisms of ROS/RNS-induced apoptosis.
- To identify key mediators and signaling pathways involved in oxidant-triggered cell death.
- To highlight the role of survival pathways, particularly the heme oxygenase-1/carbon monoxide system, in mitigating oxidative stress-induced apoptosis.
Main Methods:
- Review of existing literature on ROS/RNS, apoptosis, and oxidative stress models.
- Analysis of signaling pathways including receptor activation, caspases, Bcl-2 family proteins, and protein kinases.
- Investigation of lipid-derived mediators and cellular survival responses.
Main Results:
- ROS/RNS induce apoptosis through mechanisms involving caspase activation, mitochondrial dysfunction, and modulation by protein kinases.
- Lipid-derived mediators are identified as potential intermediates in oxidant-induced apoptosis.
- The heme oxygenase-1/carbon monoxide system is a significant intracellular antiapoptotic mechanism.
Conclusions:
- ROS/RNS play a critical role in initiating cell death pathways, contributing to disease pathogenesis.
- Understanding these mechanisms is crucial for developing therapeutic strategies against oxidative stress-related disorders.
- The heme oxygenase-1/carbon monoxide system represents a promising target for cytoprotective interventions.
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