Kaempferol Attenuates 2-Deoxy-D-ribose-Induced Oxidative Cell Damage in MC3T3-E1 Osteoblastic Cells

Suh, Kwang Sik; Choi, Eun‐Mi; Kwon, Mikwang; Chon, Suk; Oh, Seungjoon; Woo, Jeong-Taek; Kim, Sung Woon; Kim, Jin-Woo; Kim, Young Seol

doi:10.1248/bpb.32.746

Cited by 34 publications

(37 citation statements)

References 24 publications

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“…We have shown previously that the antioxidants NAC and ALA protect pancreatic β-cells and MC3T3-E1 osteoblastic cells against oxidative stress as shown by a reduction in ROS generation and apoptosis. [14][15][16]19,31) These findings indicate that apigenin can function as an antioxidant and thereby protect pancreatic β-cells from dRib-induced oxi- dative cell damage. We used JC-1 staining to assess ΔΨ m, which is a marker of mitochondrial oxidative phosphorylation activity.…”

Section: Resultsmentioning

confidence: 86%

“…19) To evaluate the effect of apigenin itself on pancreatic β-cell survival, cells were incubated in RPMI-1640 medium containing 0.5% FBS with increasing concentrations of apigenin (0.01-100 µM) for 24 h and then cell viabilities were determined using the CCK-8 assay. Apigenin at concentrations of 10 µM or lower did not influence cell viability, while higher doses (> 10 µM) were cytotoxic in a dose-dependent manner (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…We have previously demonstrated that dRib promotes apoptosis by increasing oxidative stress in HIT-T15 pancreatic β-cells [14][15][16] and MC3T3-E1 osteoblastic cells. [17][18][19] Flavonoids have been shown to exert a variety of biological effects including antioxidant, anti-inflammatory, and anticancer effects in different cell types. [20][21][22] In particular, flavonoids have been shown to have potent antidiabetic and antioxidant activity in experimental diabetes animal models.…”

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Apigenin Attenuates 2-Deoxy-D-ribose-Induced Oxidative Cell Damage in HIT-T15 Pancreatic .BETA.-Cells

Suh

Woo

et al. 2012

Biological & Pharmaceutical Bulletin

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Glucose toxicity contributes to progressive β-cell failure and the development of overt diabetes. Oxidative stress is an important aspect of glucose toxicity in pancreatic β-cells. We investigated whether the flavonoid apigenin protects pancreatic β-cells from 2-deoxy-D-ribose (dRib)-induced oxidative cell damage. HIT-T15 pancreatic β-cells were cultured with or without apigenin in the presence of dRib. Time-and dosedependent cell viability was monitored using a cell counting kit (CCK-8), while the induction of apoptosis was analyzed using a cell death enzyme-linked immunosorbent assay (ELISA) kit. Mitochondrial membrane potential (ΔΨ m ) was determined using the JC-1 kit. Intracellular oxidative stress was measured by fluorometric analysis of DCFH oxidation using 2′,7′-dichlorofluorescin diacetate (DCFH-DA) as the probe. In addition, the DNA binding activity of the oxidative stress-related transcriptional factors nuclear factor-κB (NF-κB) and activator protein 1 (AP-1) were analyzed. dRib reduced cell survival and ΔΨ m , while it markedly increased intracellular levels of reactive oxygen species (ROS), apoptosis, and the activity of the oxidative stress-related transcription factors NF-κB and AP-1. However, pretreatment of cells with apigenin attenuated all the dRib-induced effects. The anti-oxidants, N-acetyl-L-cysteine (NAC) and alpha lipoic acid (ALA), also prevented both dRib-induced oxidative damage and activation of NF-κB and AP-1. Taken together, these results suggest that apigenin attenuates dRib-induced cell damage in pancreatic β-cells via oxidative stressrelated signaling. Key words oxidative stress; apigenin; 2-deoxy-D-ribose; diabetes; pancreatic β-cellOxidative stress is known to be a major contributor to the development of overt diabetes and its associated complications.1) Oxidative stress results from a persistent imbalance between antioxidant defenses and the production of highly reactive oxygen species (ROS).2) ROS are normal byproducts of cellular metabolism. However, a marked increase in glucose metabolism could lead to excessive ROS production, which could contribute to the development of diabetic complications. In particular, pancreatic β-cells express low levels of antioxidant enzymes and do not up-regulate these enzymes upon exposure to high concentrations of glucose.3) Thus, increased ROS production in the presence of low antioxidant defense levels could result in ROS accumulation, which would lead to the oxidative pancreatic β-cell damage that is partly responsible for diabetes. Nuclear factor-κB (NF-κB) and activator protein 1 (AP-1) are 2 redox-sensitive transcription factors that can be regulated by oxidative stress. [4][5][6] By activating these transcription factors in isolated peripheral mononuclear cells of diabetic patients, ROS are also involved in the pathogenesis of diabetic nephropathy. 7) In addition, activation of NF-κB correlates with the quality of glycemic control and has been shown to be reduced by treatment with antioxidants in a diabetic animal model and diabetic pa...

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Section: Resultsmentioning

confidence: 86%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

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Apigenin Attenuates 2-Deoxy-D-ribose-Induced Oxidative Cell Damage in HIT-T15 Pancreatic .BETA.-Cells

Suh

Woo

et al. 2012

Biological & Pharmaceutical Bulletin

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“…Flavonoids are widely found in vegetables and fruits [Gerritsen et al, 1995;Bai et al, 1998], and four of the major subclasses are flavones, flavonols, isoflavones and flavanones [Havsteen, 1983], which have multiple biological and pharmacological activities owing to their anti-oxidant [Suh et al, 2009], anti-inflammatory [Hämäläinen et al, 2007] and estrogenic effects [Dang and Lowik, 2005]. Quercetin exhibits anti-tumor properties, possibly through its ability to stimulate the immune system, induce apoptosis, alter the mitotic cycle, scavenge free radicals, modify gene expression, and block angiogenesis [Hayashi et al, 2000].…”

Section: Discussionmentioning

confidence: 99%

Kaempferol stimulates bone sialoprotein gene transcription and new bone formation

Yang

Takai

Utsunomiya

et al. 2010

J of Cellular Biochemistry

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Kaempferol is a typical flavonol-type flavonoid that is present in a variety of vegetables and fruits, and has a protective effect on postmenopausal bone loss. Bone sialoprotein (BSP) is thought to function in the initial mineralization of bone and could be crucial for osteoblast differentiation, bone matrix mineralization and tumor metastasis. In the present study we investigated the regulation of BSP transcription by kaempferol in rat osteoblast-like UMR106 cells, and the effect of kaempferol on new bone formation. Kaempferol (5 microM) increased BSP and Osterix mRNA levels at 12 h and up-regulated Runx2 mRNA expression at 6 h. Kaempferol increased luciferase activity of the construct pLUC3, which including the promoter sequence between nucleotides -116 to +60. Transcriptional stimulation by kaempferol abrogated in constructs included 2 bp mutations in the inverted CCAAT, CRE, and FRE elements. Gel shift analyses showed that kaempferol increased nuclear protein binding to CRE and FRE elements, whereas the CCAAT-protein complex did not change after kaempferol stimulation. Twelve daily injections of 5 microM kaempferol directly into the periosteum of parietal bones of newborn rats increased new bone formation. These data suggest that kaempferol increased BSP gene transcription mediated through inverted CCAAT, CRE, and FRE elements in the rat BSP gene promoter, and could induce osteoblast activities in the early stage of bone formation.

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“…Cell viability was tested using a colorimetric assay based on the uptake of MTT by viable cells (20). In brief, a solution of MTT (0.5 mg/ml) was added to the cells followed by incubation at 37˚C to form blue formazan crystals.…”

Section: -(45-dimethylthiazol-2-yl)-25-diphenyltetrazolium Bromidementioning

confidence: 99%

Effect of omeprazole on the expression of transcription factors in osteoclasts and osteoblasts

Hyun

Chun²,

Keum³

et al. 2010

Int J Mol Med

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Abstract. The use of proton pump inhibitors (PPIs) seems to be related to increased fracture risk but the mechanism is unclear. In an effort to clarify the mechanism, we evaluated the effect of omeprazole, a representative of the PPIs, on the expression of transcription factors in osteoclasts and osteoblasts. Murine RAW264.7 and MC3T3-E1 cells were used for osteoclast and osteoblast analysis, to which various concentrations of omeprazole were added. RAW264.7 cells with ≥3 nuclei were considered tartrate-resistant acid phosphatase (TRAP)-positive, i.e. activated osteoclasts. Expressions of the calcitonin receptor (CTR), c-fos, nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), and matrix metalloproteinase (MMP)-9 mRNA in osteoclasts were evaluated. Gene expression of osteocalcin and of the osteoprotegerin/receptor activator of NF-κB ligand (OPG/RANKL) ratio in osteoblasts was examined and Western blotting of NFATc1 was performed. Treating the osteoclasts with increasing doses of omeprazole did not affect TRAP positivity, but significantly decreased the expressions of CTR, c-fos, NFATc1, and MMP-9 regardless of the omeprazole concentration. The expression of osteocalcin and of the OPG/RANKL ratio in osteoblasts was augmented with increasing omeprazole concentrations. The result of the Western blot analysis with NFATc1 was similar to that of the expression of NFATc1 mRNA. Omeprazole decreased the activation of osteoclasts but increased that of osteoblasts in vitro, in part causing an osteopetrosis-like effect. Together with the effect of omeprazole on calcium homeostasis, increased fracture risk may be due to the osteopetrorickets-like effect of omeprazole.

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Kaempferol Attenuates 2-Deoxy-D-ribose-Induced Oxidative Cell Damage in MC3T3-E1 Osteoblastic Cells

Cited by 34 publications

References 24 publications

Apigenin Attenuates 2-Deoxy-D-ribose-Induced Oxidative Cell Damage in HIT-T15 Pancreatic .BETA.-Cells

Apigenin Attenuates 2-Deoxy-D-ribose-Induced Oxidative Cell Damage in HIT-T15 Pancreatic .BETA.-Cells

Kaempferol stimulates bone sialoprotein gene transcription and new bone formation

Effect of omeprazole on the expression of transcription factors in osteoclasts and osteoblasts

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