Differential cell surface recruitment of the superoxide‐producing NADPH oxidases Nox1, Nox2 and Nox5: The role of the small GTPase Sar1

Kiyohara, Takuya; Miyano, Kei; Kamakura, Sachiko; Hayase, Junya; Chishiki, Kanako; Kohda, Akira; Sumimoto, Hideki

doi:10.1111/gtc.12590

Cited by 13 publications

(8 citation statements)

References 66 publications

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“…The oxidative source for both sides of the Golgi membrane has not yet been determined. We preliminarily expected the involvement of membrane-bound Noxs, which are also present on the Golgi membrane (Nox2) [38]. It is possible that a Nox inhibitor, such as VAS2870, might modulate the redox status of the Golgi membrane, which is a currently ongoing experiment.…”

Section: Discussionmentioning

confidence: 99%

Visualization of the Redox Status of Cytosolic Glutathione Using the Organelle- and Cytoskeleton-Targeted Redox Sensors

et al. 2020

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Glutathione is a small thiol-containing peptide that plays a central role in maintaining cellular redox homeostasis. Glutathione serves as a physiologic redox buffer by providing thiol electrons for catabolizing harmful oxidants and reversing oxidative effects on biomolecules. Recent evidence suggests that the balance of reduced and oxidized glutathione (GSH/GSSG) defines the redox states of Cys residues in proteins and fine-tunes their stabilities and functions. To elucidate the redox balance of cellular glutathione at subcellular resolution, a number of redox-sensitive green fluorescent protein (roGFP) variants have been developed. In this study, we constructed and functionally validated organelle- and cytoskeleton-targeted roGFP and elucidated the redox status of the cytosolic glutathione at a subcellular resolution. These new redox sensors firmly established a highly reduced redox equilibrium of cytosolic glutathione, wherein significant deviation was observed among cells. By targeting the sensor to the cytosolic and lumen sides of the Golgi membrane, we identified a prominent redox gradient across the biological membrane at the Golgi body. The results demonstrated that organelle- and cytoskeleton-targeted sensors enable the assessment of glutathione oxidation near the cytosolic surfaces of different organelle membranes.

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Section: Discussionmentioning

confidence: 99%

Visualization of the Redox Status of Cytosolic Glutathione Using the Organelle- and Cytoskeleton-Targeted Redox Sensors

et al. 2020

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“…NOX5 also shares a common core architecture with the other isoforms (27% identity with NOX2), with the addition of a N-ter extension containing 4 EF-hand motifs. NOX5 is endowed with other specificities compared to other NOX isoforms, such as a Ca 2+dependent activation, no requirement for p22 phox and cytosolic factors, and the absence of glycosylation [199,200].…”

Section: Nox5mentioning

confidence: 99%

NADPH Oxidases (NOX): An Overview from Discovery, Molecular Mechanisms to Physiology and Pathology

et al. 2021

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The reactive oxygen species (ROS)-producing enzyme NADPH oxidase (NOX) was first identified in the membrane of phagocytic cells. For many years, its only known role was in immune defense, where its ROS production leads to the destruction of pathogens by the immune cells. NOX from phagocytes catalyzes, via one-electron trans-membrane transfer to molecular oxygen, the production of the superoxide anion. Over the years, six human homologs of the catalytic subunit of the phagocyte NADPH oxidase were found: NOX1, NOX3, NOX4, NOX5, DUOX1, and DUOX2. Together with the NOX2/gp91phox component present in the phagocyte NADPH oxidase assembly itself, the homologs are now referred to as the NOX family of NADPH oxidases. NOX are complex multidomain proteins with varying requirements for assembly with combinations of other proteins for activity. The recent structural insights acquired on both prokaryotic and eukaryotic NOX open new perspectives for the understanding of the molecular mechanisms inherent to NOX regulation and ROS production (superoxide or hydrogen peroxide). This new structural information will certainly inform new investigations of human disease. As specialized ROS producers, NOX enzymes participate in numerous crucial physiological processes, including host defense, the post-translational processing of proteins, cellular signaling, regulation of gene expression, and cell differentiation. These diversities of physiological context will be discussed in this review. We also discuss NOX misregulation, which can contribute to a wide range of severe pathologies, such as atherosclerosis, hypertension, diabetic nephropathy, lung fibrosis, cancer, or neurodegenerative diseases, giving this family of membrane proteins a strong therapeutic interest.

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“…While Nox1-4 are primarily associated with the cell membrane, Nox5 localizes in intracellular compartments mainly the perinuclear area and ER (99,104,109,111). This is functionally relevant because the ER is a Ca 2+ -rich depot and the site of protein synthesis and post-translational modification.…”

Section: P22phox-independent Noxes In the Cardiovascular Systemimport...mentioning

confidence: 99%

“…This is functionally relevant because the ER is a Ca 2+ -rich depot and the site of protein synthesis and post-translational modification. Within cells, Nox5 traffics from intracellular compartments to the cell membrane bringing it into close proximity to regulatory proteins such as PKC and c-Src that influence its activation and downstream signaling (109)(110)(111)(112)(113).…”

Section: P22phox-independent Noxes In the Cardiovascular Systemimport...mentioning

confidence: 99%

Oxidative Stress and Hypertension

Griendling

Camargo

Ríos

et al. 2021

Circulation Research

305

158

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A link between oxidative stress and hypertension has been firmly established in multiple animal models of hypertension but remains elusive in humans. While initial studies focused on inactivation of nitric oxide by superoxide, our understanding of relevant reactive oxygen species (superoxide, hydrogen peroxide, and peroxynitrite) and how they modify complex signaling pathways to promote hypertension has expanded significantly. In this review, we summarize recent advances in delineating the primary and secondary sources of reactive oxygen species (nicotinamide adenine dinucleotide phosphate oxidases, uncoupled endothelial nitric oxide synthase, endoplasmic reticulum, and mitochondria), the posttranslational oxidative modifications they induce on protein targets important for redox signaling, their interplay with endogenous antioxidant systems, and the role of inflammasome activation and endoplasmic reticular stress in the development of hypertension. We highlight how oxidative stress in different organ systems contributes to hypertension, describe new animal models that have clarified the importance of specific proteins, and discuss clinical studies that shed light on how these processes and pathways are altered in human hypertension. Finally, we focus on the promise of redox proteomics and systems biology to help us fully understand the relationship between ROS and hypertension and their potential for designing and evaluating novel antihypertensive therapies.

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Differential cell surface recruitment of the superoxide‐producing NADPH oxidases Nox1, Nox2 and Nox5: The role of the small GTPase Sar1

Cited by 13 publications

References 66 publications

Visualization of the Redox Status of Cytosolic Glutathione Using the Organelle- and Cytoskeleton-Targeted Redox Sensors

Visualization of the Redox Status of Cytosolic Glutathione Using the Organelle- and Cytoskeleton-Targeted Redox Sensors

NADPH Oxidases (NOX): An Overview from Discovery, Molecular Mechanisms to Physiology and Pathology

Oxidative Stress and Hypertension

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