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Advanced oxidation protein products sensitized the transient receptor potential vanilloid 1 via NADPH oxidase 1 and 4 to cause mechanical hyperalgesia

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ABSTRACT

Oxidative stress is a possible pathogenesis of hyperalgesia. Advanced oxidation protein products (AOPPs), a new family of oxidized protein compounds, have been considered as a novel marker of oxidative stress. However, the role of AOPPs in the mechanism of hyperalgesia remains unknown. Our study aims to investigate whether AOPPs have an effect on hyperalgesia and the possible underlying mechanisms. To identify the AOPPs involved, we induced hyperalgesia in rats by injecting complete Freund’s adjuvant (CFA) in hindpaw. The level of plasma AOPPs in CFA-induced rats was 1.6-fold in comparison with what in normal rats (P<0.05). After intravenous injection of AOPPs-modified rat serum albumin (AOPPs-RSA) in Sprague-Dawley rats, the paw mechanical thresholds, measured by the electronic von Frey system, significantly declined. Immunofluorescence staining indicated that AOPPs increased expressions of NADPH oxidase 1 (Nox1), NADPH oxidase 4 (Nox4), transient receptor potential vanilloid 1 (TRPV1) and calcitonin gene-related peptide (CGRP) in the dorsal root ganglia (DRG) tissues. In-vitro studies were performed on primary DRG neurons which were obtained from both thoracic and lumbar DRG of rats. Results indicated that AOPPs triggered reactive oxygen species (ROS) production in DRG neurons, which were significantly abolished by ROS scavenger N-acetyl-l-cysteine (NAC) and small-interfering RNA (siRNA) silencing of Nox1 or Nox4. The expressions of Nox1, Nox4, TRPV1 and CGRP were significantly increased in AOPPs-induced DRG neurons. And relevant siRNA or inhibitors notably suppressed the expressions of these proteins and the calcium influxes in AOPPs-induced DRG neurons. In conclusion, AOPPs increased significantly in CFA-induced hyperalgesia rats and they activated Nox1/Nox4-ROS to sensitize TRPV1-dependent Ca2+ influx and CGRP release which led to inducing mechanical hyperalgesia.

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Related in: MedlinePlus

The paw withdrawal threshold and the concentration of plasma AOPPs in CFA-induced rats. (A) Paw mechanical threshold was tested by the electronic von Frey system after different treatment. (B) The concentration of AOPPs in plasma was detected by chloramine-T method. Data represent mean±SEM of at least three independent experiments. n=4 per group. *P<0.05 versus PBS group.
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f0005: The paw withdrawal threshold and the concentration of plasma AOPPs in CFA-induced rats. (A) Paw mechanical threshold was tested by the electronic von Frey system after different treatment. (B) The concentration of AOPPs in plasma was detected by chloramine-T method. Data represent mean±SEM of at least three independent experiments. n=4 per group. *P<0.05 versus PBS group.

Mentions: We tested the paw withdrawal threshold and measured the concentration of plasma AOPPs in CFA-induced rats. As shown in Fig. 1A, the paw withdrawal threshold declined from Day 0 (25.38±0.13 g) to Day 12 (6.90±0.27 g) and remained at a low level until Day 21 (6.54±0.29 g). Fig. 1B indicated that the level of plasma AOPPs in CFA-induced rats was 1.6-fold in comparison with that in the PBS group (P<0.05). These data indicated that AOPPs were present in CFA-induced rats..


Advanced oxidation protein products sensitized the transient receptor potential vanilloid 1 via NADPH oxidase 1 and 4 to cause mechanical hyperalgesia
The paw withdrawal threshold and the concentration of plasma AOPPs in CFA-induced rats. (A) Paw mechanical threshold was tested by the electronic von Frey system after different treatment. (B) The concentration of AOPPs in plasma was detected by chloramine-T method. Data represent mean±SEM of at least three independent experiments. n=4 per group. *P<0.05 versus PBS group.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5037245&req=5

f0005: The paw withdrawal threshold and the concentration of plasma AOPPs in CFA-induced rats. (A) Paw mechanical threshold was tested by the electronic von Frey system after different treatment. (B) The concentration of AOPPs in plasma was detected by chloramine-T method. Data represent mean±SEM of at least three independent experiments. n=4 per group. *P<0.05 versus PBS group.
Mentions: We tested the paw withdrawal threshold and measured the concentration of plasma AOPPs in CFA-induced rats. As shown in Fig. 1A, the paw withdrawal threshold declined from Day 0 (25.38±0.13 g) to Day 12 (6.90±0.27 g) and remained at a low level until Day 21 (6.54±0.29 g). Fig. 1B indicated that the level of plasma AOPPs in CFA-induced rats was 1.6-fold in comparison with that in the PBS group (P<0.05). These data indicated that AOPPs were present in CFA-induced rats..

View Article: PubMed Central - PubMed

ABSTRACT

Oxidative stress is a possible pathogenesis of hyperalgesia. Advanced oxidation protein products (AOPPs), a new family of oxidized protein compounds, have been considered as a novel marker of oxidative stress. However, the role of AOPPs in the mechanism of hyperalgesia remains unknown. Our study aims to investigate whether AOPPs have an effect on hyperalgesia and the possible underlying mechanisms. To identify the AOPPs involved, we induced hyperalgesia in rats by injecting complete Freund&rsquo;s adjuvant (CFA) in hindpaw. The level of plasma AOPPs in CFA-induced rats was 1.6-fold in comparison with what in normal rats (P&lt;0.05). After intravenous injection of AOPPs-modified rat serum albumin (AOPPs-RSA) in Sprague-Dawley rats, the paw mechanical thresholds, measured by the electronic von Frey system, significantly declined. Immunofluorescence staining indicated that AOPPs increased expressions of NADPH oxidase 1 (Nox1), NADPH oxidase 4 (Nox4), transient receptor potential vanilloid 1 (TRPV1) and calcitonin gene-related peptide (CGRP) in the dorsal root ganglia (DRG) tissues. In-vitro studies were performed on primary DRG neurons which were obtained from both thoracic and lumbar DRG of rats. Results indicated that AOPPs triggered reactive oxygen species (ROS) production in DRG neurons, which were significantly abolished by ROS scavenger N-acetyl-l-cysteine (NAC) and small-interfering RNA (siRNA) silencing of Nox1 or Nox4. The expressions of Nox1, Nox4, TRPV1 and CGRP were significantly increased in AOPPs-induced DRG neurons. And relevant siRNA or inhibitors notably suppressed the expressions of these proteins and the calcium influxes in AOPPs-induced DRG neurons. In conclusion, AOPPs increased significantly in CFA-induced hyperalgesia rats and they activated Nox1/Nox4-ROS to sensitize TRPV1-dependent Ca2+ influx and CGRP release which led to inducing mechanical hyperalgesia.

No MeSH data available.


Related in: MedlinePlus