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Published on: August 2, 2018
Genetically Encoded Tools for Research of Cell Signaling and Metabolism under Brain Hypoxia
Alexander I Kostyuk1,2, Aleksandra D Kokova1,2, Oleg V Podgorny1,2,3
1Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, 117997 Moscow, Russia.
Abstract:
Hypoxia is characterized by low oxygen content in the tissues. The central nervous system (CNS) is highly vulnerable to a lack of oxygen. Prolonged hypoxia leads to the death of brain cells, which underlies the development of many pathological conditions. Despite the relevance of the topic, different approaches used to study the molecular mechanisms of hypoxia have many limitations. One promising lead is the use of various genetically encoded tools that allow for the observation of intracellular parameters in living systems. In the first part of this review, we provide the classification of oxygen/hypoxia reporters as well as describe other genetically encoded reporters for various metabolic and redox parameters that could be implemented in hypoxia studies. In the second part, we discuss the advantages and disadvantages of the primary hypoxia model systems and highlight inspiring examples of research in which these experimental settings were combined with genetically encoded reporters.
Insights
Genetically encoded reporters offer a promising approach to study cellular hypoxia and its effects on the central nervous system (CNS). These tools help overcome limitations in current methods for observing molecular mechanisms during low oxygen conditions.
Area of Science:
- Biochemistry
- Neuroscience
- Molecular Biology
Background:
- Hypoxia, or low tissue oxygen, severely impacts the central nervous system (CNS), leading to brain cell death and various pathologies.
- Current methods for studying hypoxia's molecular mechanisms face significant limitations.
- Genetically encoded tools offer a novel way to observe intracellular parameters in living systems.
Purpose of the Study:
- To classify oxygen/hypoxia reporters and other genetically encoded metabolic/redox reporters for hypoxia research.
- To discuss the advantages and disadvantages of primary hypoxia model systems.
- To showcase research integrating these reporters with hypoxia models.
Main Methods:
- Review and classification of existing genetically encoded oxygen/hypoxia reporters.
- Description of other relevant genetically encoded metabolic and redox reporters.
- Analysis of primary hypoxia model systems and their limitations.
Main Results:
- A classification of genetically encoded reporters applicable to hypoxia studies is presented.
- The review details various reporters for metabolic and redox parameters useful in hypoxia research.
- Advantages and disadvantages of common hypoxia models are discussed, with examples of their use with reporters.
Conclusions:
- Genetically encoded reporters are valuable tools for advancing the study of hypoxia.
- Combining these reporters with established hypoxia models enhances research capabilities.
- This approach offers a promising direction for understanding CNS vulnerability to low oxygen.

