Vesicular nucleotide transporter mediates ATP release and migration in neutrophils

Harada, Yuka; Kato, Yuri; Miyaji, Takaaki; Omote, Hiroshi; Moriyama, Yoshinori; Hiasa, Miki

doi:10.1074/jbc.m117.810168

Cited by 27 publications

(13 citation statements)

References 38 publications

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“…Some studies have evidenced that Nrf2 could potentially enhance the synthesis of ATP in various cell models [62,63]. As ATP is crucial for PMN migration [64], we thus hypothesized that ATP could be involved in the modified migration observed in Nrf2 KO PMNs. However, we failed to evidence a significant difference between ATP levels in resting WT and Nrf2 KO PMNs suggesting that Nrf2 plays a weak role in this setting.…”

Section: Discussionmentioning

confidence: 93%

Nrf2 downregulates zymosan-induced neutrophil activation and modulates migration

et al. 2019

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Polymorphonuclear neutrophils (PMNs) are the first line of defense against pathogens and their activation needs to be tightly regulated in order to limit deleterious effects. Nrf2 (Nuclear factor (erythroïd-derived 2)-like 2) transcription factor regulates oxidative stress and/or represses inflammation in various cells such as dendritic cells or macrophages. However, its involvement in PMN biology is still unclear. Using Nrf2 KO mice, we thus aimed to investigate the protective role of Nrf2 in various PMN functions such as oxidative burst, netosis, migration, cytokine production and phagocytosis, mainly in response to zymosan. We found that zymosan induced Nrf2 accumulation in PMNs leading to the upregulation of some target genes including Hmox-1 , Nqo1 and Cat . Nrf2 was able to decrease zymosan-induced PMN oxidative burst; sulforaphane-induced Nrf2 hyperexpression confirmed its implication. Tnfα , Ccl3 and Cxcl2 gene transcription was decreased in zymosan-stimulated Nrf2 KO PMNs, suggesting a role for Nrf2 in the regulation of proinflammatory cytokine production. However, Nrf2 was not involved in phagocytosis. Finally, spontaneous migration of Nrf2 KO PMNs was lower than that of WT PMNs. Moreover, in response to low concentrations of CXCL2 or CXCL12, Nrf2 KO PMN migration was decreased despite similar CXCR2 and CXCR4 expression and ATP levels in PMNs from both genotypes. Nrf2 thus seems to be required for an optimal migration. Altogether these results suggest that Nrf2 has a protective role in several PMN functions. In particular, it downregulates their activation in response to zymosan and is required for an adequate migration.

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Section: Discussionmentioning

confidence: 93%

Nrf2 downregulates zymosan-induced neutrophil activation and modulates migration

et al. 2019

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“…The SLC17A9 protein is a VNUT that participates in transporting nucleotides [8]. As a VNUT, the SLC17A9 protein plays an important role in transporting ATP in airway neutrophils as well as epithelial, astrocyte, adrenal chromaffin and pancreatic cells [6][7][8]19,20]. Cao et al [9] have shown that SLC17A9 functions as a lysosomal ATP transporter and maintains cell viability.…”

Section: Discussionmentioning

confidence: 99%

“…The SLC17A9 protein is associated with cell migration, and SLC17A9 knockdown decreases cell migration in human lung cancer cells [22]. The VNUT is responsible for vesicular ATP release and neutrophil migration [20]. Also, microglial migration is mediated by ATP release from lysosomes [26].…”

Section: Discussionmentioning

confidence: 99%

High SLC17A9 Expression Correlates with Poor Survival in Gastric Carcinoma

Deng

et al. 2019

Future Oncol.

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Aim: To elucidate the clinicopathological significance and prognostic value of SLC17A9 expression in gastric carcinoma (GC). Methods: SLC17A9 mRNA level and its relationship with TP53 mutation was analyzed. SLC17A9 protein expression was examined by immunohistochemistry in 161 patients. Results: SLC17A9 mRNA and protein expression were higher in GC tissues than in adjacent normal tissues (p < 0.01). SLC17A9 mRNA expression was higher in GC tissues having mutated TP53 than in tissues with wild-type TP53 (p < 0.001). High SLC17A9 expression was also significantly associated with poor overall survival and recurrence-free survival and was also found to be an independent prognostic factor for long-term survival in GC patients.Conclusion: Our results show that SLC17A9 may serve as a potential prognostic biomarker in GC patients.

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“…Decreased cell viability was observed in PHEKs at high UVB energies (100 mJ/cm 2 , 200 mJ/cm 2 ), whereas cytotoxicity was not detected in PHEMs at up to 200 mJ/ cm 2 of UVB (Figures 1b, 1d). In addition to ATP release, vesicular nucleotide transporter (VNUT) staining was utilized to observe UVB-induced intracellular ATP accumulation, as VNUT is a key molecule for ATP storage and exocytosis upon stimulation (Harada et al, 2018). UVB radiation at high energies (100 mJ/cm 2 , 200 mJ/cm 2 ) increased VNUT staining intensity in keratinocytes and melanocytes relative to control levels (Figures 2a, 2b).…”

Section: Uvb-induced Atp Release In Primary Human Epidermal Keratinocmentioning

confidence: 99%

Critical Role of ATP-P2X7 Axis in UV-Induced Melanogenesis

Lee

Kim

Ahn

et al. 2019

Journal of Investigative Dermatology

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Purinergic signaling participates in skin physiology and pathology, such as hair growth, wound healing, inflammation, pain, and skin cancer. However, few studies have investigated the involvement of purinergic signaling in skin pigmentation. This study demonstrated that extracellular adenosine 5 0-triphosphate (ATP) released from keratinocytes by UVB radiation promotes melanin production in primary human epidermal melanocytes and ex vivo skin cultures. Intracellular calcium ion and protein kinase C/CREB signaling contributed to ATP-mediated melanogenesis. Also, P2X7 receptor was proven to play a pivotal role in ATPmediated melanogenesis because P2X7 receptor blockade abrogated ATP-induced melanin production. In addition, MNT1 cells with P2X7 receptor knockout using CRISPR/Cas9 system did not show any increase in MITF expression when co-cultured with UV-irradiated keratinocytes compared to MNT1 cells with intact P2X7 receptor, which showed increased expression of MITF. In conclusion, our results indicate that the extracellular ATP-P2X7 signaling axis is an adjunctive mechanism in UV-induced melanogenesis. Furthermore, ATP-induced purinergic signaling in melanocytes may alter skin pigmentation.

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Vesicular nucleotide transporter mediates ATP release and migration in neutrophils

Cited by 27 publications

References 38 publications

Nrf2 downregulates zymosan-induced neutrophil activation and modulates migration

Nrf2 downregulates zymosan-induced neutrophil activation and modulates migration

High SLC17A9 Expression Correlates with Poor Survival in Gastric Carcinoma

Critical Role of ATP-P2X7 Axis in UV-Induced Melanogenesis

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