Tumor necrosis factor-α down-regulates human Cu/Zn superoxide dismutase 1 promoter via JNK/AP-1 signaling pathway

Afonso, Valéry; Santos, Guilherme; Collin, Pascal; Khatib, Abdel‐Majid; Mitrović, D; Lomri, Noureddine; Leitman, Dale C.; Lomri, Abderrahim

doi:10.1016/j.freeradbiomed.2006.05.014

Cited by 61 publications

(55 citation statements)

References 66 publications

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“…Oxidative stresses such as reactive oxygen species upregulates Cu/Zn-SOD as the defensive mechanism (54), but little is known about the inhibitory factors. Recently, Afonso et al (1) showed that TNF-␣ downregulates Cu/Zn-SOD promoter via JNK/AP-1 signaling pathway in U937 cells. Our in vitro study utilizing RPTEC showed the potential role of TNF-␣ in the suppression of Cu/Zn-SOD gene in renal tubular cells among various stimuli.…”

Section: Discussionmentioning

confidence: 99%

Chronic hypoxia aggravates renal injury via suppression of Cu/Zn-SOD: a proteomic analysis

Son¹,

Kojima²,

Inagi³

et al. 2008

American Journal of Physiology-Renal Physiology

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Son D, Kojima I, Inagi R, Matsumoto M, Fujita T, Nangaku M. Chronic hypoxia aggravates renal injury via suppression of Cu/Zn-SOD: a proteomic analysis. Am J Physiol Renal Physiol 294: F62-F72, 2008. First published October 24, 2007 doi:10.1152/ajprenal.00113.2007.-Accumulating evidence suggests a pathogenic role of chronic hypoxia in various kidney diseases. Chronic hypoxia in the kidney was induced by unilateral renal artery stenosis, followed 7 days later by observation of tubulointerstitial injury. Proteomic analysis of the hypoxic kidney found various altered proteins. Increased proteins included lipocortin-5, calgizzarin, ezrin, and transferrin, whereas the decreased proteins were ␣ 2u-globulin PGCL1, eukaryotic translation elongation factor 1␣ 2, and Cu/Zn superoxide dismutase (SOD1). Among these proteins, we focused on Cu/Zn-SOD, a crucial antioxidant. Western blot analysis and real-time quantitative PCR analysis confirmed the downregulation of Cu/Zn-SOD in the chronic hypoxic kidney. Furthermore, our laser capture microdissection system showed that the expression of Cu/Zn-SOD was predominant in the tubulointerstitium and was decreased by chronic hypoxia. The tubulointerstitial injury estimated by histology and immunohistochemical markers was ameliorated by tempol, a SOD mimetic. This amelioration was associated with a decrease in levels of the oxidative stress markers 4-hydroxyl-2-nonenal and nitrotyrosine. Our in vitro studies utilizing cultured tubular cells revealed a role of TNF-␣ in downregulation of Cu/Zn-SOD. Since the administration of anti-TNF-␣ antibody ameliorated Cu/Zn-SOD suppression, TNF-␣ seems to be one of the suppressants of Cu/Zn-SOD. In conclusion, our proteomic analysis revealed a decrease in Cu/Zn-SOD, at least partly by TNF-␣, in the chronic hypoxic kidney. This study, for the first time, uncovered maladaptive suppression of Cu/Zn-SOD as a mediator of a vicious cycle of oxidative stress and subsequent renal injury induced by chronic hypoxia. chronic kidney failure; oxidative stress ONCE RENAL DAMAGE REACHES a certain threshold, the progression of renal disease is consistent, irreversible and largely independent of the initial insult. The final common pathway in this process has been closely studied. The chronic hypoxia hypothesis, proposed by Fine et al. (11), emphasizes chronic ischemic damage in the tubulointerstitium as a final common pathway in end-stage kidney injury. Since its introduction, this fascinating hypothesis has been intensively investigated by many investigators (9,20,24). Despite intensive efforts to elucidate the pathomechanisms of chronic hypoxia on kidney damage, however, their complexity has hampered investigations and details remain scarce. Among others, mechanisms proposed to date include transdifferentiation (22), cell death (40 -42), production of extracellular matrix (26,27), and so on.Advances in proteomics technology offer promise to substantially improve our understanding and treatment of the molecular basis of disease. In particular, deciphering the a...

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Section: Discussionmentioning

confidence: 99%

Chronic hypoxia aggravates renal injury via suppression of Cu/Zn-SOD: a proteomic analysis

Son¹,

Kojima²,

Inagi³

et al. 2008

American Journal of Physiology-Renal Physiology

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“…The hmsod1 promoter also contained a copy of xenobiotic response element (XRE; TNGCGTG) in the proximal region (145-bp from the start codon in a reverse orientation). Although the specific roles of these factors in the orchestration of the sod1 gene expression remain to be explored in teleosts, many of them are known to be involved in the transcriptional regulation of mammalian sod1s under stimulatory or inflammatory conditions (Rojo et al, 2004;Afonso et al, 2006). Thus, extensive examinations of hmsod1 expression in response to designed stress treatments or immune challenges are needed to better hypothesize the specific or coordinated roles of these transcription factors.…”

Section: Characteristics Of the 5'-flanking Regulatory Regionmentioning

confidence: 99%

Characterization of Copper/Zinc-Superoxide Dismutase (Cu/Zn-SOD) Gene from an Endangered Freshwater Fish Species Hemibarbus mylodon (Teleostei; Cypriniformes)

Lee¹,

Kim²,

Bang³

et al. 2011

Fisheries and aquatic sciences

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Gene structure of copper/zinc-superoxide dismutase (Cu/Zn-SOD; sod1) was characterized in Hemibarbus mylodon (Teleostei; Cypriniformes), an endangered freshwater fish species in Korean peninsula. Full-length cDNA of H. mylodon SOD1 consisted of a 796-bp open reading frame sequence encoding 154 amino acids, and the deduced polypeptide sequence shared high sequence homology with other orthologs, particularly with regard to metal-coordinating ligands. Genomic structure of the H. mylodon sod1 gene (hmsod1; 1,911 bp from the ATG start codon to the stop codon) was typical quinquepartite (i.e., five exons interrupted by four introns); the lengths of the exons were similar among species belonging to various taxonomic positions. The molecular phylogeny inferred from sod1 genes in the teleost lineage was in accordance with the conventional taxonomic assumptions. 5'-flanking upstream region of hmsod1, obtained using the genome walking method, contained typical TATA and CAAT boxes. It also showed various transcription factor binding motifs that may be potentially involved in stress/immune response (e.g., sites for activating proteins or nuclear factor kappa B) or metabolism of xenobiotic compounds (e.g., xenobiotic response element; XRE). The hmsod1 transcripts were ubiquitously detected among tissues, with the liver and spleen showing the highest and lowest expression, respectively. An experimental challenge with Edwardsiella tarda revealed significant upregulation of the hmsod1 in kidney (4.3-fold) and spleen (3.1-fold), based on a real-time RT-PCR assay. Information on the molecular characteristics of this key antioxidant enzyme gene could be a useful basis for a biomarker-based assay to understand cellular stresses in this endangered fish species.

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“…Moreover, inflammation and ROS generation are now evident to go hand to hand in a number of pathological manifestations, wherein, TNF-α has been found to play a regulatory role [35,36]. In case of brain disorders also, neuroinflammation and excitotoxicity have been found to be responsible for triggering neuro-excitotoxic disorders/diseases like; traumatic brain injury, Ischemia, Alzheimers disease, Parkinson's disease, etc [17,[37][38][39][40][41][42][43][44][45][46][47].…”

Section: Discussionmentioning

confidence: 99%

Resveratrol Normalizes Hyperammonemia Induced Pro-Inflammatory and Pro-Apoptotic Conditions in Rat Brain

Khanna¹,

Trigun²

2016

IJCAM

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Research ArticleInt J Complement Alt Med 2016, 4(2): 00115 IntroductionAmmonia neurotoxicity is considered responsible for development of a serious nervous system disorder called hepatic encephalopathy (HE). This situation arises mainly due to liver dysfunction led hyperammonemia (HA). HE is characterized by the neuropsychiatric manifestations related to motor dysfunction, memory impairment, and deranged sleep-awake cycle [1,2]. Since HE affects the quality of life of the patients, it is important to develop effective therapeutic strategy against HE. This necessitates understanding the neuro-chemistry of HA pathogenesis.Since ammonia crosses the blood brain barrier easily, prolonged HA condition, a common situation during chronic liver failure (CLF), is likely to maintain increased ammonia concentration in brain [3,4]. The information, mainly derived from the cell culture system and from animal models with acute HE, suggest that the increased brain ammonia level mainly drives astrocytes to undergo significant morpho-pathological changes and also over activates glutamate-NMDA receptor (N-Methyl-D-Aspartate Receptor) pathway in the post-synaptic neurons [1,[5][6][7]. Moreover, NMDAR inhibition could not be translated into prevention of ammonia neurotoxicity, mainly because threshold glutamate-NMDAR activation is necessary for normal neurological functions including higher order brain functions and normal synaptic activity.During recent past, "TNF theory" (Tumor necrosis factor) of HE pathogenesis could draw much attention due to a close association between the level of TNF-α and ammonia in the brain of CLF patients with HE [8]. Later studies have also emphasized significant involvement of TNF-α and other cytokines in HE to the extent that these cytokines could be used as markers for encephalopathy grading [4,[9][10][11][12][13].It is now evident that the microglia and astroglia cells in brain synthesize TNF-α to regulate higher order brain functions and astrocyte induced synaptic strengthening [14][15][16][17]. However, when produced in higher amounts during neuropathology, they are known to potentiate glutamate induced cytotoxicity by inhibiting glutamate transport to the glial cells from the synaptic cleft [12,[16][17][18][19]. Even development of MHE has been described to be dependent more on enhanced inflammatory markers than the severity of CLF or HA in the CLF patients [20]. Moreover, some findings from in vitro studies suggest that resveratrol treatment could prevent ammonia toxicity in astroglial cells by normalizing ROS/RNS level [12,21,22]. Thus, hinting towards a significant role of resveratrol in ameliorating ammonia toxicity. However, the mechanism by which resveratrol does so is unclear.Resveratrol (3, 3, 4'-trihydroxy-Trans stilbene), a natural polyphenol, is found in a number of dietary sources such as grapes, berries, and red wine [23][24][25]. It acts as an effective cardioprotector, AbstractChronic liver failure (CLF) led hyperammonemia (HA) is known to develop a metabolic brain disorder known a...

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Tumor necrosis factor-α down-regulates human Cu/Zn superoxide dismutase 1 promoter via JNK/AP-1 signaling pathway

Cited by 61 publications

References 66 publications

Chronic hypoxia aggravates renal injury via suppression of Cu/Zn-SOD: a proteomic analysis

Chronic hypoxia aggravates renal injury via suppression of Cu/Zn-SOD: a proteomic analysis

Characterization of Copper/Zinc-Superoxide Dismutase (Cu/Zn-SOD) Gene from an Endangered Freshwater Fish Species Hemibarbus mylodon (Teleostei; Cypriniformes)

Resveratrol Normalizes Hyperammonemia Induced Pro-Inflammatory and Pro-Apoptotic Conditions in Rat Brain

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