Oxidants induce transcriptional activation of manganese superoxide dismutase in glomerular cells

Yoshioka, Toshima; Homma, Toshio; Meyrick, Barbara; Takeda, Michio; Moore-Jarrett, Tracy; Kon, Valentina; Ichikawa, Iekuni
August 1994
Kidney International;Aug1994, Vol. 46 Issue 2, p405
Academic Journal
Oxidants induce transcriptional activation of manganese superoxide dismutase in glomerular cells. Cultured rat glomerular mesangial and epithelial cells and bovine glomerular endothelial cells were exposed to various concentrations of hydrogen peroxide (H2O2). Mesangial cells treated with 10 to 100 μM H2O2 for 24 hours showed a two- to ninefold increase in Mn-SOD mRNA expression associated with significantly (P < 0.005) increased Mn-SOD activity (22.2 ± 1.2 and 12.2 ± 0.7 μ/mg protein for H2O2 100 μM treated and untreated cells, respectively). In contrast, expression of Cu-Zn SOD and β-actin mRNA was not affected by H2O2. Induction of Mn-SOD mRNA by H2O2 was inhibited by actinomycin-D (4 μM) treatment. Glomerular endothelial cells also showed an increase in Mn-SOD mRNA expression following 100 μM H2O2 treatment, as did glomerular epithelial cells following treatment with 500 and 1000 μM H2O2 but not with 100 μM. Transcriptional activity of the Mn-SOD gene was assessed with a fusion reporter gene consisting of a luciferase gene (pGL2P) and a 1.2 kb fragment from the rat Mn-SOD genomic DNA (−806 to +408 bp of the transcription initiation site, −806: +408). The construct was transfected into rat glomerular mesangial and epithelial cells. Mesangial and epithelial cells transfected with pGL2P (−806: +44)8) and treated with H2O2 (100 μM and 1 mM for mesangial and epithelial cells, respectively) demonstrated some threefold increase in luciferase activity, whereas cells transfected with pGL2P lacking the Mn-SOD fragment did not show changes in luciferase activity following H2O2 treatment. Other oxidants, namely or α- and β-naphthoflavone (50 μM to mesangial cells) and puromycin aminonucleoside (25 to 50 μg/ml to epithelial cells), also induced transcriptional activation (2- to 5-fold increase) in these cells. Thus. Mn-SOD levels in glomerular cells arc enhanced when they arc exposed to oxidant stress, and this up-regulation involves transcriptional activation. Further, the Mn-SOD gene contains enhancer clement(s) which respond to diverse oxidant stress. The inducibility by oxidants of local Mn-SOD demonstrates that glomerular SOD may play a decisive role in the pathogenesis of glomerular injuries in which the balance between oxidants and antioxidants is critical.


Related Articles

  • Preferential selection of MnSOD transcripts in proliferating normal and cancer cells. Chaudhuri, L; Nicholson, A M; Kalen, A L; Goswami, P C // Oncogene;3/8/2012, Vol. 31 Issue 10, p1207 

    Manganese superoxide dismutase (MnSOD) is a nuclear encoded and mitochondrial matrix-localized redox enzyme that is known to regulate the cellular redox environment. Cellular redox environment changes during transitions between quiescent and proliferative cycles. Human MnSOD has two poly(A)...

  • Escherichia coli avoids high dissolved oxygen stress by activation of SoxRS and manganesesuperoxide dismutase. Baez, Antonino; Shiloach, Joseph // Microbial Cell Factories;2013, Vol. 12 Issue 1, p1 

    Background: High concentrations of reactive oxygen species (ROS) were reported to cause oxidative stress to E. coli cells associated with reduced or inhibited growth. The high ROS concentrations described in these reports were generated by exposing the bacteria to H2O2 and superoxide-generating...

  • Hereditary disorders of the glomerular basement membrane. Smeets, H. J. M.; Knoers, V. V. A. M.; van de Heuvel, L. P. W. J.; Lemmink, H. H.; Schröder, C. H.; Monnens, L. A. H. // Pediatric Nephrology;1996, Vol. 10 Issue 6, p779 

    Increased knowledge of the biochemical composition of the glomerular basement membrane (GBM) and the introduction of molecular genetics has shed new light on the hereditary disorders of the GBM. In this review three disorders are highlighted. About 85% of the cases reported as Alport syndrome...

  • Steroid-resistant nephrotic focal segmental glomerulosclerosis: a treatable disease. Tune, Bruce M.; Lieberman, Ellin; Mendoza, Stanley A. // Pediatric Nephrology;1996, Vol. 10 Issue 6, p772 

    If not aggressively treated, oral steroid-resistant (SRst) nephrotic focal segmental glomerulosclerosis (FSGS) is likely to progress to end-stage renal failure. Three observations challenge the conclusion of the International Study of Kidney Diseases in Children (ISKDC) that SRst FSGS is...

  • Anti-glomerular basement membrane glomerulopathy in a young child. Boven, K.; Miljoen, H. P. J.; Hoeck, K. J. Van; Marck, E. A. Van; Acker, K. J. Van // Pediatric Nephrology;1996, Vol. 10 Issue 6, p745 

    We report the youngest patient with anti-glomerular basement membrane disease described in the literature to date. Age-dependent expression of the target antigen in this auto-immune disease explains the low incidence in young children. Despite adequate immunosuppression, renal function did not...

  • Decreased Expression of Manganese Superoxide Dismutase in Transformed Cells Is Associated with Increased Cytosine Methylation of the SOD2 Gene. Huang, Yuanhui; He, Tongrong; Domann, Frederick E. // DNA & Cell Biology;Aug99, Vol. 18 Issue 8, p643 

    Tumor cells express lower levels of manganese superoxide dismutase (MnSOD) than their normal counterparts. Enforced expression of MnSOD reverses the malignant phenotype of many transformed cells, suggesting that SOD2 is a tumor suppressor. The SOD2 gene contains a large CpG island spanning >3.5...

  • Suppressive effects of Sairei-to on mesangial proliferation in a rat model of glomerulonephritis. Liu, Ning; Makino, Toshiaki; Honda, Gisho; Muso, Eri; Kita, Toru; Ono, Takahiko // Clinical & Experimental Nephrology;Sep2004, Vol. 8 Issue 3, p216 

    Background. Sairei-to (TJ-114) is a Japanese herbal medicine of standardized quality, originating from traditional Chinese medicine. In the present in vivo study, we investigated the suppressive effects of TJ-114, Shosaiko-to (TJ-9), and Saiboku-to (TJ-96) on mesangioproliferative...

  • TPA-Activated Transcription of the Human MnSOD Gene: Role of Transcription Factors SP-1 and Egr-1. Porntadavity, Sureerut; Xu, Yong; Kiningham, Kelley; Rangnekar, Vivek M.; Prachayasitikul, Virapong; St. Clair, Daret K. // DNA & Cell Biology;Aug2001, Vol. 20 Issue 8, p473 

    Induction of manganese superoxide dismutase (MnSOD) in response to oxidative stress has been well established in animals, tissues, and cell culture. However, the role of the human MnSOD (hMnSOD) promoter in stimulus-dependent activation of transcription is unknown. The hMnSOD promoter lacks both...

  • Galloway-Mowat syndrome: a glomerular basement membrane disorder? Lin, Chun-Chen; Tsai, Jeng-Daw; Lin, Shuan-Pei; Tzen, Chin-Yuan; Shen, Ein-Yiao; Shih, Chien-Sheng // Pediatric Nephrology;Aug2001, Vol. 16 Issue 8, p653 

    We report a female infant with Galloway-Mowat syndrome. In addition to the characteristic dysmorphic appearance, neurological anomalies and early-onset nephrotic syndrome, she had arachnodactyly, an observation thus far reported uniquely in Taiwan. Also, her elder sister had the same condition....


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics