Calcium sensing receptor activates the NLRP3 inflammasome via a chaperone-assisted degradative pathway involving Hsp70 and LC3-II

Gutiérrez-López, Tania Yareli; Orduña-Castillo, Lennis Beatríz; Hernández-Vásquez, Magda Nohemí; Vázquez‐Prado, José; Reyes‐Cruz, Guadalupe

doi:10.1016/j.bbrc.2018.10.028

Cited by 15 publications

(8 citation statements)

References 29 publications

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“…11 Among posttranscriptional modifications, ubiquitination and autophagy represent new potential strategies for regulating NLRP3. 14,15 The ubiquitin proteasome system (UPS) and autophagy serve as two major clearance systems in humans, and their roles are removing necrotic tissue and abnormally accumulated proteins; the overactivated inflammasome is a potential target of these processes. 12 Chong's result has shown that the ubiquitination of NLRP3 is associated with the activation of the NLRP3 inflammasome.…”

Section: Introductionmentioning

confidence: 99%

Zinc provides neuroprotection by regulating NLRP3 inflammasome through autophagy and ubiquitination in a spinal contusion injury model

Lin¹,

Tian

Zhao

et al. 2020

CNS Neurosci Ther

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Section: Introductionmentioning

confidence: 99%

Zinc provides neuroprotection by regulating NLRP3 inflammasome through autophagy and ubiquitination in a spinal contusion injury model

Lin¹,

Tian

Zhao

et al. 2020

CNS Neurosci Ther

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“…Previous studies have reported that CaSR modulates autophagy in THP-1 macrophages [ 20 ], cardiac fibroblasts [ 21 ] and kidney cells [ 22 ]. The association between CaSR and autophagy in AT has only been recently explored [ 3 ], and our present findings further contribute to understanding well-known autophagy dysregulation in AT of people with obesity.…”

Section: Discussionmentioning

confidence: 99%

“…Liu et al observed in vitro that CaSR inhibition reduces cardiac hypertrophy by decreasing autophagy [ 18 , 19 ]. Several studies have confirmed that CaSR activation increases autophagy in THP-1 macrophages [ 20 ], cardiac fibroblasts [ 21 ] and kidney cells [ 22 ]. We recently reported that cinacalcet elevates autophagy in human preadipocytes [ 3 ], which may be part of the mechanistic scaffold involved in inflammation-linked AT dysfunction that induces obesity-related diseases.…”

Section: Introductionmentioning

confidence: 99%

Calcium-Sensing Receptor in Adipose Tissue: Possible Association with Obesity-Related Elevated Autophagy

Mattar

Sanhueza

Yuri

et al. 2020

IJMS

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Autophagy is upregulated in adipose tissue (AT) from people with obesity. We showed that activation of the calcium-sensing receptor (CaSR) elevates proinflammatory cytokines through autophagy in preadipocytes. Our aim is to understand the role of CaSR on autophagy in AT from humans with obesity. We determined mRNA and protein levels of CaSR and markers of autophagy by qPCR and western blot in human visceral AT explants or isolated primary preadipocytes (60 donors: 72% female, 23–56% body fat). We also investigated their association with donors’ anthropometric variables. Donors’ % body fat and CaSR mRNA expression in AT were correlated (r = 0.44, p < 0.01). CaSR expression was associated with mRNA levels of the autophagy markers atg5 (r = 0.37, p < 0.01), atg7 (r = 0.29, p < 0.05) and lc3b (r = 0.40, p < 0.01). CaSR activation increased becn and atg7 mRNA expression in AT. CaSR activation also upregulated LC3II by ~50%, an effect abolished by the CaSR inhibitor. Spermine (CaSR agonist) regulates LC3II through the ERK1/2 pathway. Structural equation model analysis suggests a link between donors’ AT CaSR expression, AT autophagy and expression of Tumor Necrosis Factor alpha TNF-α. CaSR expression in visceral AT is directly associated with % body fat, and CaSR activation may contribute to obesity-related disruption in AT autophagy.

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“…The CaSR modulates NLRP3 inflammasome activation via changes in intracellular Ca 2+ and cyclic AMP concentrations [30]. Activation of proteasome-and lysosome-dependent mechanisms by the CaSR promotes the degradation of key modulators of NLRP inflammasome activation [31]. Recently, Bruton's tyrosine kinase (BTK) has been reported to play a role in physiological inhibition of NLRP3 inflammasome activation, which explains why patients with X-linked agammaglobulinemia tend to develop Crohn's disease (CD) [32].…”

Section: Nlrp3 Inflammasome Regulatorsmentioning

confidence: 99%

Contradictory Effects of NLRP3 Inflammasome Regulatory Mechanisms in Colitis

Wagatsuma

Nakase

2020

IJMS

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The inflammasome is an intracellular molecular complex, which is mainly involved in innate immunity. Inflammasomes are formed in response to danger signals, associated with infection and injury, and mainly regulate the secretion of interleukin-1β and interleukin-18. Inflammasome dysregulation is known to be associated with various diseases and conditions, and its regulatory mechanisms have become of great interest in recent years. In the colon, inflammasomes have been reported to be associated with autophagy and the microbiota, and their dysregulation contributes to colitis and. However, the detailed role of inflammasomes in inflammatory bowel disease is still under debate because the mechanisms that regulate the inflammasome are complex and the inflammasome components and cytokines show seemingly contradictory multiple effects. Herein, we comprehensively review the literature on inflammasome functioning in the colon and describe the complex interactions of the Nod-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome components with inflammatory cytokines, autophagy, and the microbiota in experimental colitis models and patients with inflammatory bowel disease.

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Calcium sensing receptor activates the NLRP3 inflammasome via a chaperone-assisted degradative pathway involving Hsp70 and LC3-II

Cited by 15 publications

References 29 publications

Zinc provides neuroprotection by regulating NLRP3 inflammasome through autophagy and ubiquitination in a spinal contusion injury model

Zinc provides neuroprotection by regulating NLRP3 inflammasome through autophagy and ubiquitination in a spinal contusion injury model

Calcium-Sensing Receptor in Adipose Tissue: Possible Association with Obesity-Related Elevated Autophagy

Contradictory Effects of NLRP3 Inflammasome Regulatory Mechanisms in Colitis

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