-nitrosoglutathione reductase (GSNOR) is a well-known regulator in controlling protein -nitrosylation modification and nitric oxide (NO) homeostasis. Here, a GSNOR inhibitor N6022 and silencing were applied to investigate the roles of SlGSNOR in tomato fruit postharvest ripening. We found that the application of N6022 and -nitrosoglutathione (GSNO, a NO donor), and silencing delayed the transition of fruit skin color by improving total chlorophyll level by 88.57%, 44.78%, and 91.03%, respectively. Meanwhile, total carotenoid and lycopene contents were reduced by these treatments. Concurrently, the activity of chlorophyll biosynthesis enzymes and the expression of related genes were upregulated, and the transcript abundances of total carotenoid bioproduction genes were downregulated, by N6022 and GSNO treatments and silencing. In addition, fruit softening was postponed by N6022, GSNO, and silencing, through delaying the decrease of firmness and declining cell wall composition; structure-related enzyme activity; and gene expression levels. Furthermore, N6022, GSNO, and silencing enhanced the accumulation of titratable acid; ascorbic acid; total phenol; and total flavonoid, but repressed the content of soluble sugar and soluble protein accompanied with the expression pattern changes of nutrition-related genes. In addition, the endogenous NO contents were elevated by 197.55%; 404.59%; and 713.46%, and the endogenous SNOs contents were enhanced by 74.65%; 93.49%; and 94.85%; by N6022 and GSNO treatments and silencing, respectively. Altogether, these results indicate that SlGSNOR positively promotes tomato postharvest fruit ripening, which may be largely on account of its negative roles in the endogenous NO level.
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http://dx.doi.org/10.3390/ijms25052729 | DOI Listing |
Neuroscience
January 2025
Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC, USA. Electronic address:
Previously, we reported that both S-nitrosoglutathione (GSNO), a carrier of cellular nitric oxide, and N6022, an injectable form of GSNO reductase (GSNOR) inhibitor that increases endogenous GSNO levels, alleviate experimental autoimmune encephalomyelitis (EAE) in mice by suppressing Th1 and Th17 immune responses. Building on these findings, we explored the role of GSNOR in EAE pathogenesis and evaluated the efficacy of an orally active GSNOR inhibitor (N91115) in treating the EAE disease. EAE mice exhibited heightened expression/activity of GSNOR in the spinal cord, and the knockout of the GSNOR gene resulted in much milder clinical manifestations of EAE, with lower degrees of demyelination and axonal loss, reduced microglial and astrocyte activations, as well as suppressed Th1 and Th17 cell responses, alongside bolstered Treg immune responses.
View Article and Find Full Text PDFInt J Mol Sci
February 2024
College of Horticulture, Gansu Agricultural University, 1 Yinmen Village, Anning District, Lanzhou 730070, China.
-nitrosoglutathione reductase (GSNOR) is a well-known regulator in controlling protein -nitrosylation modification and nitric oxide (NO) homeostasis. Here, a GSNOR inhibitor N6022 and silencing were applied to investigate the roles of SlGSNOR in tomato fruit postharvest ripening. We found that the application of N6022 and -nitrosoglutathione (GSNO, a NO donor), and silencing delayed the transition of fruit skin color by improving total chlorophyll level by 88.
View Article and Find Full Text PDFFront Pharmacol
December 2023
Department of Pediatrics, Medical University of South Carolina, Charleston, SC, United States.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which initially surfaced in late 2019, often triggers severe pulmonary complications, encompassing various disease mechanisms such as intense lung inflammation, vascular dysfunction, and pulmonary embolism. Currently, however, there's no drug addressing all these mechanisms simultaneously. This study explored the multi-targeting potential of S-nitrosoglutathione (GSNO) and N6022, an inhibitor of GSNO reductase (GSNOR) on markers of inflammatory, vascular, and thrombotic diseases related to COVID-19-induced acute lung disease.
View Article and Find Full Text PDFRedox Biol
September 2021
Department of Pediatrics, Medical University of South Carolina, Charleston, SC, USA; Research Service, Ralph H. Johnson Veterans Administration Medical Center, Charleston, SC, USA. Electronic address:
B cells play both protective and pathogenic roles in T cell-mediated autoimmune diseases by releasing regulatory vs. pathogenic cytokines. B cell-depleting therapy has been attempted in various autoimmune diseases but its efficacy varies and can even worsen symptoms due to depletion of B cells releasing regulatory cytokines along with B cells releasing pathogenic cytokines.
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