Emerging new role of NFAT5 in inducible nitric oxide synthase in response to hypoxia in mouse embryonic fibroblast cells

Serman, Yair; Fuentealba, Rodrigo A.; Pastén, Consuelo; Rocco, Jocelyn; Ko, Ben C.B.; Carrión, Flavio; Irarrázabal, Carlos E.

doi:10.1152/ajpcell.00054.2019

Cited by 8 publications

(8 citation statements)

References 39 publications

(53 reference statements)

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“…In in vitro models, Xu et al, 51 induced the expression of iNOS by oxygen and glucose deprivation, showing an increase starting from 2 h with a maximum expression at 6 h. In addition, they identified cell death by apoptosis with an increase corresponding to the duration of deprivation. For their part, Serman et al, 52 induced the expression of iNOS at different times of hypoxia identifying an increase after 4 h and reaching a plateau at 8 h of hypoxia. Several studies have shown that hypoxia induces the expression of iNOS, leading to rapid production of NO.…”

Section: Discussionmentioning

confidence: 99%

Bioelectric, tissue, and molecular characteristics of the gastric mucosa at different times of ischemia

Peña-Mercado

García-Lorenzana

César

et al. 2021

Exp Biol Med (Maywood)

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Gastrointestinal ischemia may be presented as a complication associated with late shock detection in patients in critical condition. Prolonged ischemia can cause mucosal integrity to lose its barrier function, triggering alterations that can induce organ dysfunction and lead to death. Electrical impedance spectroscopy has been proposed to identify early alteration in ischemia-induced gastric mucosa in this type of patients. This work analyzed changes in impedance parameters, and tissue and molecular alterations that allow us to identify the time of ischemia in which the gastric mucosa still maintains its barrier function. The animals were randomly distributed in four groups: Control, Ischemia 60, 90, and 120 min. Impedance parameters were measured and predictive values were determined to categorize the degree of injury using a receiver operating characteristic curve. Markers of inflammatory process and apoptosis (iNOS, TNFα, COX-2, and Caspase-3) were analyzed. The largest increase in impedance parameters occurred in the ischemia 90 and 120 min groups, with resistance at low frequencies (RL) and reactance at high frequencies (XH) being the most related to damage, allowing prediction of the occurrence of reversible and irreversible tissue damage. Histological analysis and apoptosis assay showed progressive mucosal deterioration with irreversible damage ( p < 0.001) starting from 90 min of ischemia. Furthermore, a significant increase in the expression of iNOS, TNFα, and COX-2 was identified in addition to apoptosis in the gastric mucosa starting from 90 min of ischemia. Tissue damage generated by an ischemia time greater than 60 min induces loss of barrier function in the gastric mucosa.

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Section: Discussionmentioning

confidence: 99%

Bioelectric, tissue, and molecular characteristics of the gastric mucosa at different times of ischemia

Peña-Mercado

García-Lorenzana

César

et al. 2021

Exp Biol Med (Maywood)

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“…The experimental process was carried out according to how we describe before [35]. In brief, total RNA was isolated using a RNeasy Mini Kit (Cat Nº: 74104, Qiagen) according to the manufacturer's directions.…”

Section: Real-time Pcrmentioning

confidence: 99%

1400W Prevents Renal Injury in the Renal Cortex But Not in the Medulla in a Murine Model of Ischemia and Reperfusion Injury.

Pastén

Lozano

Méndez³

et al. 2022

Cell Physiol Biochem

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Background/Aims: Acute kidney injury (AKI) carries high morbidity and mortality, and the inducible nitric oxide synthase (iNOS) is a potential molecular target to prevent kidney dysfunction. In previous work, we reported that the pharmacological inhibitions of iNOS before ischemia/reperfusion (I/R) attenuate the I/R-induced AKI in mice. Here, we study the iNOS inhibitor 1400W [N-(3-(Aminomethyl)benzyl] acetamide, which has been described to be much more specific to iNOS inhibition than other compounds. Methods: We used 30 minutes of bilateral renal ischemia, followed by 24 hours of reperfusion in Balb/c mice. 1400w (10 mg/kg i.p) was applied before I/R injury. We measured the expression of elements associated with kidney injury, inflammation, macrophage polarization, mesenchymal transition, and nephrogenic genes by qRT-PCR in the renal cortex and medulla. The Periodic Acid-Schiff (PAS) was used to study the kidney morphology. Results: Remarkably, we found that 1400W affects the renal cortex and medulla in different ways. Thus, in the renal cortex, 1400W prevented the I/R-upregulation of 1. NGAL, Clusterin, and signs of morphological damage; 2. IL-6 and TNF-α; 3. TGF-β; 4. M2(Arg1, Erg2, cMyc) and M1(CD38, Fpr2) macrophage polarization makers; and 5. Vimentin and FGF2 levels but not in the renal medulla. Conclusion: 1400W conferred protection in the kidney cortex compared to the kidney medulla. The present investigation provides relevant information to understand the opportunity to use 1400W as a therapeutic approach in AKI treatment.

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“…The protocol was conducted as it was described previously [23,27]. In brief, the total RNA was isolated using an RNeasy Mini Kit (Qiagen) according to the manufacturer's directions.…”

Section: Real-time Pcrmentioning

confidence: 99%

The Ischemia and Reperfusion Injury Involves the Toll-Like Receptor-4 Participation Mainly in the Kidney Cortex

2022

Cell Physiol Biochem

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BACKGROUND/AIMS: The renal inflammatory response and kidney regeneration in ischemia-reperfusion injury (IRI) are associated with Toll-like receptor 4 (TLR4). Here we study the role of TLR4 during IRI in the renal cortex and medulla separately, using wild-type (TLR4-WT) and Knockout (TLR4-KO) TLR4 mice. METHODS: We used 30 minutes of bilateral renal ischemia, followed by 48 hours of reperfusion in C57BL/6 mice. We measured the expression of elements associated with kidney injury, inflammation, macrophage polarization, mesenchymal transition, and proteostasis in the renal cortex and medulla by qRT-PCR and Western blot. In addition, we studied kidney morphology by H/E and PAS. RESULTS: Renal ischemia (30min) and reperfusion (48hrs) induced the mRNA and protein of TLR4 in the renal cortex. In addition, Serum Creatinine (SCr), blood urea nitrogen (BUN), Neutrophil gelatinase-associated lipocalin (NGAL), and acute tubular necrosis (ATN) were increased in TLR4-WT by IRI. Interestingly, the SCr and BUN had normal levels in TLR-KO during IRI. However, ATN and high levels of NGAL were present in the kidneys of TLR4-KO mice. The pro-inflammatory (IL-6 and TNF-α) and anti-inflammatory (Foxp3 and IL-10) markers increased by IRI only in the cortex of TLR4-WT but not in TLR4-KO mice. Furthermore, the M1 (CD38 and Frp2) and M2 (Arg-I, Erg-2, and c-Myc) macrophage markers increased by IRI only in the cortex of TLR4-WT. The TLR4-KO blunted the IRI-upregulation of M1 but not the M2 macrophage polarization. Vimentin increased in the renal cortex and medulla of TLR4-WT animals but not in the cortex of TLR4-KO mice. In addition, iNOS and clusterin were increased by IRI only in the cortex of TLR4-WT, and the absence of TLR4 inhibited only clusterin upregulation. Finally, Hsp27 and Hsp70 protein levels increased by IRI in the cortex and medulla of TLR4-WT and TRL4-KO lost the IRI-upregulation of Hsp70. In summary, TLR4 participates in renal ischemia and reperfusion through pro-inflammatory and anti-inflammatory responses inducing impaired kidney function (SCr and BUN). However, the IRI-upregulation of M2 macrophage markers (cortex), iNOS (cortex), IL-6 (medulla), vimentin (medulla), and Hsp27 (cortex and medulla) were independent of TLR4. CONCLUSION: The TLR4 inactivation during IRI prevented the loss of renal function due to the inactivation of inflammation response, avoiding M1 and preserving the M2 macrophage polarization in the renal cortex.

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Emerging new role of NFAT5 in inducible nitric oxide synthase in response to hypoxia in mouse embryonic fibroblast cells

Cited by 8 publications

References 39 publications

Bioelectric, tissue, and molecular characteristics of the gastric mucosa at different times of ischemia

Bioelectric, tissue, and molecular characteristics of the gastric mucosa at different times of ischemia

1400W Prevents Renal Injury in the Renal Cortex But Not in the Medulla in a Murine Model of Ischemia and Reperfusion Injury.

The Ischemia and Reperfusion Injury Involves the Toll-Like Receptor-4 Participation Mainly in the Kidney Cortex

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