Abstract
Intracellular redox imbalance is mainly caused by overproduction of reactive oxygen species (ROS) or weakness of the natural antioxidant defense system. It is involved in the pathophysiology of a wide array of human diseases. Hydrogen sulfide (H2S) is now recognized as the third “gasotransmitters” and proved to exert a wide range of physiological and cytoprotective functions in the biological systems. Among these functions, the role of H2S in oxidative stress has been one of the main focuses over years. However, the underlying mechanisms for the antioxidant effect of H2S are still poorly comprehended. This review presents an overview of the current understanding of H2S specially focusing on the new understanding and mechanisms of the antioxidant effects of H2S based on recent reports. Both inhibition of ROS generation and stimulation of antioxidants are discussed. H2S-induced S-sulfhydration of key proteins (e.g., p66Shc and Keap1) is also one of the focuses of this review.
Highlights
In 1777, a young Swedish apothecary, Carl Wilhelm Scheele, treated ferrous sulfide with a mineral acid and noted a colorless gas with a characteristic odor of rotten eggs
Cystathionine β-synthase CH1 (CBS) is primarily expressed in various regions of the brain and is essential to the production of H2S in the central nervous system [2,3,4], whereas cystathionine γlyase (CSE) is mainly expressed in the cardiovascular system [5, 6]
Calvert et al demonstrated that H2S increased the expression of Trx-1 and mediated cardioprotection through Nrf2 signaling [83]. These results demonstrate that Nrf2 is the potential endogenous cardioprotective signal in the process of cellular nonenzymatic antioxidant generation induced by H2S (Figure 4)
Summary
In 1777, a young Swedish apothecary, Carl Wilhelm Scheele, treated ferrous sulfide with a mineral acid and noted a colorless gas with a characteristic odor of rotten eggs. Nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase (NOX) is another important enzyme for intracellular ROS generation It is mainly distributed in the plasma membrane surface of phagocyte and catalyzes the one-electron reduction of oxygen to produce superoxide-free radical by utilizing NADPH as an electron donor (Figure 2). Free radicals play an important role in some physiological reactions, such as cell signal transduction and regulation of muscle tone [23, 40], excessive free radicals would cause damage to the lipids, proteins, and DNA and give rise to cellular and metabolic disturbance [30]. There are enzymes and chemical scavengers that could be used to remove excessive oxygen-free radicals formed in a living body [47]. Chemical antioxidants usually go into effect with the cooperation of antioxidant enzymes [55]
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