Expression Profiling of Crystal-Induced Injury in Human Kidney Epithelial Cells

Liang, Li; Chen, Jianmin; Vittal, Ragini; Selvanayagam, Zachariah; McAteer, James A.; Deng, Li; Tischfield, Jay A.; Chin, Khew‐Voon; Sahota, Amrik

doi:10.1159/000090503

Cited by 14 publications

(14 citation statements)

References 93 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This may be the reason why our EGϩLE rats showed more tubular cell damage, poor Ccr, and more CaOx deposition in the kidneys. In summary, this in vivo study confirmed findings in cell line studies (18,24) that oxalate and CaOx crystals increase the production of free radicals in the kidneys and result in tubular damage and increased lipid peroxidation. However, in the chronic hyperoxaluric model, a low-vitamin E diet not only increases free radical production but also decreases activities and levels of renal antioxidative enzymes.…”

Section: Discussionsupporting

confidence: 87%

Low-vitamin E diet exacerbates calcium oxalate crystal formation via enhanced oxidative stress in rat hyperoxaluric kidney

Huang¹,

Chieh²

2009

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

Huang HS, Ma MC, Chen J. Low-vitamin E diet exacerbates calcium oxalate crystal formation via enhanced oxidative stress in rat hyperoxaluric kidney. Am J Physiol Renal Physiol 295: F34-F45, 2008. First published September 17, 2008 doi:10.1152/ajprenal.90309.2008.-Vitamin E was previously reported to reduce calcium oxalate (CaOx) crystal formation. This study explored whether vitamin E deficiency affects intrarenal oxidative stress and accelerates crystal deposition in hyperoxaluria. The control (C) group of rats received a standard diet and drinking water, while the experimental groups received 0.75% ethylene glycol (EG) in drinking water for 42 days. Of the latter, one group received a standard diet (EG group), one received a low-vitamin E (LE) diet (EGϩLE group), and the last received an LE diet with vitamin E supplement (4 mg) (EGϩLEϩE group). The CϩLE and CϩLEϩE groups were the specific controls for the last two experimental groups, respectively. In a separate experiment, EG and EGϩLE rats were studied on days 3-42 to examine the temporal relationship between oxidative change and crystal formation. Urinary biochemistry and activity/levels of antioxidative and oxidative enzymes in glomeruli and tubulointerstitial specimens (TIS) were examined. In EG rats, CaOx crystal accumulation was associated with low antioxidative enzyme activity in TIS and with increased oxidative enzyme expression in glomeruli. In the EGϩLE group, marked changes in antioxidative and oxidative enzyme levels were seen and correlated with massive CaOx deposition and tubular damage. The increased oxidative stress seen with EGϩLE treatment was largely reversed by vitamin E supplementation. A temporal study showed that decrease in antioxidative defense and increased free radical formation in the EGϩLE group occurred before crystal deposition. This study shows that low vitamin E disrupts the redox balance and causes cell death, thereby favoring crystal formation. antioxidative proteins; free radicals; hyperoxaluria CALCIUM OXALATE (CaOx) crystal formation is a multifaceted and complex process that involves a series of chemical, physical, biochemical, and physiological events (6, 10, 16). The principal causative agent for the formation of calcium salt crystals is thought to be supersaturation that causes the precipitation of salts in urine. However, even though urine is supersaturated with calcium and oxalate ions in normal subjects, stones do not form because of the presence of inhibitors and other unknown mechanisms (22).Membrane injury is suggested to be the primary event in CaOx crystal binding, and oxalate-induced free radicals are significant causative factors in membrane injury (11,12,25). This injury leads to lipid and protein peroxidation and altered biochemical reactions, including depletion of the antioxidant defense system (25). On the basis of these findings, we hypothesized that if renal tubular injury due to increased oxidative stress caused by hyperoxaluria can be prevented, CaOx crystal accumulation in the kidneys can also be ...

show abstract

Section: Discussionsupporting

confidence: 87%

Low-vitamin E diet exacerbates calcium oxalate crystal formation via enhanced oxidative stress in rat hyperoxaluric kidney

Huang¹,

Chieh²

2009

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

show abstract

“…The expression of DNA ligase I, III and IV genes was measured with a quantitative real time PCR assay as previously reported (27). Expression levels were calculated as a ratio of the mRNA level for a given gene relative to the mRNA level for glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in the same cDNA sample.…”

Section: Methodsmentioning

confidence: 99%

Human DNA ligases I and III, but not ligase IV, are required for microhomology-mediated end joining of DNA double-strand breaks

Liang

Deng

Nguyen

et al. 2008

Nucleic Acids Research

123

View full text Add to dashboard Cite

DNA nonhomologous end-joining (NHEJ) and homologous recombination are two distinct pathways of DNA double-strand break repair in mammalian cells. Biochemical and genetic studies showed that DNA ends can also be joined via microhomology-mediated end joining (MHEJ), especially when proteins responsible for NHEJ, such as Ku, are reduced or absent. While it has been known that Ku-dependent NHEJ requires DNA ligase IV, it is unclear which DNA ligase(s) is required for Ku-independent MHEJ. In this study, we used a cell-free assay to determine the roles of DNA ligases I, III and IV in MHEJ and NHEJ. We found that siRNA mediated down-regulation of DNA ligase I or ligase III in human HTD114 cells led to impaired end joining that was mediated by 2-, 3- or 10-bp microhomology. In addition, nuclear extract from human fibroblasts harboring a mutation in DNA ligase I displayed reduced MHEJ activity. Furthermore, treatment of HTD114 nuclear extracts with an antibody against DNA ligase I or III also significantly reduced MHEJ. These data indicate that DNA ligases I and III are required in MHEJ. DNA ligase IV, on the contrary, is not required in MHEJ but facilitates Ku-dependent NHEJ. Therefore, MHEJ and NHEJ require different DNA ligases.

show abstract

“…Total RNA from isolated splenic lymphocytes was purified using the RNeasy kit (Qiagen, Valencia, CA) and reverse transcribed using the TaqMan reverse transcription reagent kit (Applied Biosystems, Foster City, CA). The expression of selected genes was quantified as previously reported (18). Expression levels were calculated as a ratio of the mRNA level for a given gene relative to the mRNA level for glyceraldehyde-3-phosphate dehydrogenase in the same cDNA.…”

Section: Methodsmentioning

confidence: 99%

Reduced Apoptosis and Increased Deletion Mutations at Aprt Locus In vivo in Mice Exposed to Repeated Ionizing Radiation

et al. 2007

Self Cite

View full text Add to dashboard Cite

Exposure to ionizing radiation (IR) is a risk factor for carcinogenesis because it is a mutagen. However, a single 4-Gy whole body X-ray exposure only induced a modest increase of mutations at the Aprt reporter gene locus in mouse T cells. Intriguingly, when the same dose of IR was given in a fractionated protocol (1 Gy Â 4 at weekly intervals), there was a strong induction of Aprt mutations in T cells. Many of these were mutations that arose via interstitial deletions inclusive of Aprt or by intragenic deletions. We hypothesized that the weekly fractionated X-ray exposures select for somatic cells with reduced p53 expression and/or reduced apoptosis, which, in turn, may have facilitated the accumulation of interstitial deletions, as in p53-deficient mice. We indeed found that splenocytes of mice with three previous exposures (1 Gy Â 4 in total) were more resistant to X-ray-induced apoptosis than those of mice exposed to X-rays for the first time (1 Gy total). Thus, repeated X-ray radiation selects for reduced apoptosis in vivo. However, this reduced apoptosis is p53-independent, because p53 induction and the up-regulation of genes downstream of p53, such as Bax and p21, were similar between the 1-Gy and 1 Gy Â 4 groups. Reduced apoptosis probably allows the generation of more mutations, particularly deletion mutations. Because both reduced apoptosis and increased somatic mutation are risk factors for carcinogenesis, they may contribute to the paradigm in which different radiation exposure schemes are varied in their efficiency in inducing lymphomagenesis. [Cancer Res 2007;67(5):1910-7]

show abstract

Expression Profiling of Crystal-Induced Injury in Human Kidney Epithelial Cells

Cited by 14 publications

References 93 publications

Low-vitamin E diet exacerbates calcium oxalate crystal formation via enhanced oxidative stress in rat hyperoxaluric kidney

Low-vitamin E diet exacerbates calcium oxalate crystal formation via enhanced oxidative stress in rat hyperoxaluric kidney

Human DNA ligases I and III, but not ligase IV, are required for microhomology-mediated end joining of DNA double-strand breaks

Reduced Apoptosis and Increased Deletion Mutations at Aprt Locus In vivo in Mice Exposed to Repeated Ionizing Radiation

Contact Info

Product

Resources

About