17
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Lipid Peroxidation and Its Role in the Expression of NLRP1a and NLRP3 Genes in Testicular Tissue of Male Rats: A Model of Spinal Cord Injury

      research-article

      Read this article at

          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background:

          The majority of male patients with spinal cord injury (SCI) suffer from infertility. Nucleotide-binding oligomerization domain-like receptors NOD-like receptors (NLRs) are a kind of receptors that corporate in the inflammasome complex. Recent studies have introduced the inflammasome as the responsible agent for secreting cytokines in semen. Reactive oxygen species (ROS) is one of the elements that trigger inflammasome activation. Genital infections in SCI can lead to ROS generation. We investigated the relation between lipid peroxidation and inflammasome complex activity in testicular tissue of SCI rats.

          Methods:

          Adult male rats (n=20), weighting 200-250 g, were included and divided into four groups: three experimental groups, including SCI1, SCI3, and SCI7, i.e. the rats were subjected to SCI procedure and sacrificed after one, three, and seven days, respectively and a control group. We performed a moderate, midline spinal contusion injury at thoracic level 10. The animals were anesthetized, and testes were collected for measurement of gene expression by real-time PCR. Caudal parts of epididymis were collected for malondialdehyde (MDA) measurement.

          Results:

          No NLRP1a mRNA overexpression was seen in the testes of control and SCI groups. After seven days from SCI surgery, NLRP3 mRNA expression was significantly increased in SCI7 animals ( p ≤ 0.05). There was a significant difference in MDA level in SCI7 versus control group, as well as SCI1 and SCI3 animals ( p ≤ 0.05).

          Conclusion:

          NLRP3 overexpression occurs due to the increased ROS production in testis tissue of SCI rats

          Related collections

          Most cited references40

          • Record: found
          • Abstract: found
          • Article: not found

          NLRP3 inflammasome activation: The convergence of multiple signalling pathways on ROS production?

          The NLR family, pyrin domain-containing 3 (NLRP3) inflammasome is a multiprotein complex that activates caspase 1, leading to the processing and secretion of the pro-inflammatory cytokines interleukin-1beta (IL-1beta) and IL-18. The NLRP3 inflammasome is activated by a wide range of danger signals that derive not only from microorganisms but also from metabolic dysregulation. It is unclear how these highly varied stress signals can be detected by a single inflammasome. In this Opinion article, we review the different signalling pathways that have been proposed to engage the NLRP3 inflammasome and suggest a model in which one of the crucial elements for NLRP3 activation is the generation of reactive oxygen species (ROS).
            • Record: found
            • Abstract: found
            • Article: not found

            Syk kinase signalling couples to the Nlrp3 inflammasome for anti-fungal host defence.

            Fungal infections represent a serious threat, particularly in immunocompromised patients. Interleukin-1beta (IL-1beta) is a key pro-inflammatory factor in innate antifungal immunity. The mechanism by which the mammalian immune system regulates IL-1beta production after fungal recognition is unclear. Two signals are generally required for IL-1beta production: an NF-kappaB-dependent signal that induces the synthesis of pro-IL-1beta (p35), and a second signal that triggers proteolytic pro-IL-1beta processing to produce bioactive IL-1beta (p17) via Caspase-1-containing multiprotein complexes called inflammasomes. Here we demonstrate that the tyrosine kinase Syk, operating downstream of several immunoreceptor tyrosine-based activation motif (ITAM)-coupled fungal pattern recognition receptors, controls both pro-IL-1beta synthesis and inflammasome activation after cell stimulation with Candida albicans. Whereas Syk signalling for pro-IL-1beta synthesis selectively uses the Card9 pathway, inflammasome activation by the fungus involves reactive oxygen species production and potassium efflux. Genetic deletion or pharmalogical inhibition of Syk selectively abrogated inflammasome activation by C. albicans but not by inflammasome activators such as Salmonella typhimurium or the bacterial toxin nigericin. Nlrp3 (also known as NALP3) was identified as the critical NOD-like receptor family member that transduces the fungal recognition signal to the inflammasome adaptor Asc (Pycard) for Caspase-1 (Casp1) activation and pro-IL-1beta processing. Consistent with an essential role for Nlrp3 inflammasomes in antifungal immunity, we show that Nlrp3-deficient mice are hypersusceptible to Candida albicans infection. Thus, our results demonstrate the molecular basis for IL-1beta production after fungal infection and identify a crucial function for the Nlrp3 inflammasome in mammalian host defence in vivo.
              • Record: found
              • Abstract: found
              • Article: not found

              Activation and Regulation of NLRP3 Inflammasome by Intrathecal Application of SDF-1a in a Spinal Cord Injury Model.

              Stromal cell-derived factor-1 alpha (SDF-1a) or CXCL12 is an important cytokine with multiple functions in the brain during development and in adulthood. The inflammatory response initiated by spinal cord injury (SCI) involves the processing of interleukin-1beta (IL-1ß) and IL-18 mediated by caspase-1 which is under the control of an intracellular multiprotein complex termed inflammasome. Using an SCI rat model, we found improved functional long-term recovery which is paralleled by a reduction of apoptosis after intrathecal treatment with SDF-1a. An intriguing aspect is that SDF-1a changed the number of neuroinflammatory cells in the damaged area. We further examined the cellular localization and sequential expression of several inflammasomes during SCI at 6 h, 24 h, 3 days, and 7 days as well as the role of SDF-1a as a regulatory factor for inflammasomes. Using 14-week old male Wistar rats, spinal cord contusion was applied at the thoracic segment 9, and animals were subsequently treated with SDF-1a via intrathecal application through an osmotic pump. SCI temporally increased the expression of the inflammasomes NLRP3, ASC, the inflammatory marker tumor necrosis factor-a (TNF-a), interleukin-1ß (IL-1β) and IL-18. SDF-1a significantly reduced the levels of IL-18, IL-1b, TNF-a, NLRP3, ASC, and caspase-1. Immunofluorescence double-labeling demonstrated that microglia and neurons are major sources of the ASC and NLRP3 respectivley. Our data provide clear evidence that SCI stimulates a complex scenario of inflammasome activation at the injured site and that SDF-1a-mediated neuroprotection presumably depends on the attenuation of the inflammasome complex.

                Author and article information

                Journal
                Iran Biomed J
                Iran. Biomed. J
                Iranian Biomedical Journal
                Pasteur Institute (Iran )
                1028-852X
                2008-823X
                May 2018
                : 22
                : 3
                : 151-159
                Affiliations
                [1 ]Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
                [2 ]Department of Embryology, Royan Institiute, Tehran, Iran
                [3 ]Department of Urology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
                [4 ]Department of Anatomy, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran
                [5 ]Research Center of Nervous System Stem Cells, Department of Anatomy, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran
                [6 ]School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran
                [7 ]Institute of Neuroanatomy, RWTH Aachen University, Aachen, Germany
                Author notes
                Corresponding Author: Gholamreza Hassanzadeh Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Tel.: (+98-21) 88953008; Fax.: (+98-21) 66419072; E-mail: hassanzadeh@ 123456tums.ac.ir
                Article
                IBJ-22-151
                10.22034/ibj.22.3.151
                5889500
                29034676
                07833483-f42f-4b00-8184-aac81e383b92
                Copyright: © Iranian Biomedical Journal

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License, ( http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 12 June 2017
                : 17 July 2017
                : 24 July 2017
                Categories
                Full Length

                infertility,lipid peroxidation,testis,spinal cord injuries

                Comments

                Comment on this article

                Related Documents Log