Reactive oxygen species induced by uric acid promote NRK‑52E cell apoptosis through the NEK7‑NLRP3 signaling pathway

Li, Dongdong; Wang, Luobing; Ou, Jiaoying; Wang, Chuanxu; Zhou, Jiaoyan; Lü, Lili; Wu, Yanshneg; Gao, Jiandong

doi:10.3892/mmr.2021.12368

Cited by 10 publications

(9 citation statements)

References 51 publications

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“…These findings may imply that serum UA levels in an appropriate range were associated with better outcome in patients with AIS but may be harmful when too high or too low. This is consistent with the results of preclinical studies that UA may exert a neuroprotective efficacy as an antioxidant in low concentration 48 49 , while it may become harmful as a precursor of oxygen free radicals in its higher concentration 50 51 . From this perspective, it may be more important to determine and maintain the optima ranges of serum UA which is associated with a favorable cognitive and functional outcome in patients with AIS.…”

Section: Discussionsupporting

confidence: 91%

Uric Acid and Cognitive Impairment in Patients with Acute Ischemic Stroke: A Meta-Analysis

et al. 2022

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Serum uric acid (UA) has been suggested to be correlated with outcomes after stroke. We performed a meta-analysis to evaluate the association between serum UA and post-stroke cognitive impairment (PSCI) in patients with acute ischemic stroke (AIS). Relevant observational studies were identified by search of electronic databases including PubMed, Embase, and Web of Science. A randomized-effect model incorporating the possible between-study heterogeneity was used to pool the results. Overall, eleven studies with 4246 patients of AIS were included, 2073 (48.8%) of them had PSCI. Pooled results showed that patients with PSCI had significantly higher level of serum UA as compared to those without PSCI (mean difference: 35.70 μmol/l, 95% confidence interval (CI): 8.36 to 63.01, p=0.01; I2=95%). Subgroup analysis showed significant higher level of serum UA in patients with PSCI evaluated during follow-up of 3 months to 3 years, but not for those evaluated during hospitalization (p for subgroup difference=0.01). In addition, results of meta-analysis also showed that compared to patients with lower serum UA, AIS patients with higher serum UA had increased risk of PSCI (odds ratio: 1.33, 95% CI: 1.02 to 1.73, p=0.04; I2=72%). Higher level of serum UA after disease onset may be a marker of increased risk of PSCI in patients with AIS. Although these findings need to be validated in large-scale prospective studies, the possible mechanisms underlying the association between UA and PSCI should be also investigated.

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Section: Discussionsupporting

confidence: 91%

Uric Acid and Cognitive Impairment in Patients with Acute Ischemic Stroke: A Meta-Analysis

et al. 2022

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“…Moreover, the enhancement of Nrf2 levels decreases apoptosis, attributed to NLPR3 inflammasome blocking [ 260 ]. Another protein that activates NLRP3 is never in mitosis gene A (NIMA)-related kinase 7 (NEK7) [ 261 ]. NEK7 participates in NLRP3 complex assembly, acting as a selective regulator of NLRP3 [ 262 ].…”

Section: Inflammasome Components In Ckdmentioning

confidence: 99%

“…NEK7 participates in NLRP3 complex assembly, acting as a selective regulator of NLRP3 [ 262 ]. In this sense, the in vitro model uric acid (UA)-induced urolithiasis shows that UA causes ROS overproduction, which activates NEK7, triggering NLRP3 complex assembly [ 261 ].…”

Section: Inflammasome Components In Ckdmentioning

confidence: 99%

Involvement of Inflammasome Components in Kidney Disease

et al. 2022

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Inflammasomes are multiprotein complexes with an important role in the innate immune response. Canonical activation of inflammasomes results in caspase-1 activation and maturation of cytokines interleukin-1β and -18. These cytokines can elicit their effects through receptor activation, both locally within a certain tissue and systemically. Animal models of kidney diseases have shown inflammasome involvement in inflammation, pyroptosis and fibrosis. In particular, the inflammasome component nucleotide-binding domain-like receptor family pyrin domain containing 3 (NLRP3) and related canonical mechanisms have been investigated. However, it has become increasingly clear that other inflammasome components are also of importance in kidney disease. Moreover, it is becoming obvious that the range of molecular interaction partners of inflammasome components in kidney diseases is wide. This review provides insights into these current areas of research, with special emphasis on the interaction of inflammasome components and redox signalling, endoplasmic reticulum stress, and mitochondrial function. We present our findings separately for acute kidney injury and chronic kidney disease. As we strictly divided the results into preclinical and clinical data, this review enables comparison of results from those complementary research specialities. However, it also reveals that knowledge gaps exist, especially in clinical acute kidney injury inflammasome research. Furthermore, patient comorbidities and treatments seem important drivers of inflammasome component alterations in human kidney disease.

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“…Nek7 further limits the NLRP3 inflammasome to interphase [ 171 ]. Nek7 and NLRP3 have both been found to have increased expression in response to ROS and are believed to function in inducing apoptosis [ 172 ].…”

Section: Mammalian Nek6 and Nek7mentioning

confidence: 99%

In Mitosis You Are Not: The NIMA Family of Kinases in Aspergillus, Yeast, and Mammals

Bachus

Graves

Fulham

et al. 2022

IJMS

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The Never in mitosis gene A (NIMA) family of serine/threonine kinases is a diverse group of protein kinases implicated in a wide variety of cellular processes, including cilia regulation, microtubule dynamics, mitotic processes, cell growth, and DNA damage response. The founding member of this family was initially identified in Aspergillus and was found to play important roles in mitosis and cell division. The yeast family has one member each, Fin1p in fission yeast and Kin3p in budding yeast, also with functions in mitotic processes, but, overall, these are poorly studied kinases. The mammalian family, the main focus of this review, consists of 11 members named Nek1 to Nek11. With the exception of a few members, the functions of the mammalian Neks are poorly understood but appear to be quite diverse. Like the prototypical NIMA, many members appear to play important roles in mitosis and meiosis, but their functions in the cell go well beyond these well-established activities. In this review, we explore the roles of fungal and mammalian NIMA kinases and highlight the most recent findings in the field.

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Reactive oxygen species induced by uric acid promote NRK‑52E cell apoptosis through the NEK7‑NLRP3 signaling pathway

Cited by 10 publications

References 51 publications

Uric Acid and Cognitive Impairment in Patients with Acute Ischemic Stroke: A Meta-Analysis

Uric Acid and Cognitive Impairment in Patients with Acute Ischemic Stroke: A Meta-Analysis

Involvement of Inflammasome Components in Kidney Disease

In Mitosis You Are Not: The NIMA Family of Kinases in Aspergillus, Yeast, and Mammals

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