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AYGUN, CANAN/0000-0002-7955-5943 WOS: 000393323800007 PubMed: 28123334 Aim: The adequacy of 50 mcg folic acid supplementation given to low-birth-weight babies was investigated. The folate levels of the mothers and infants, and breastmilk, and the optimum dose for folic acid supplementation were also investigated. Material and Methods: After obtaining blood from 141 low-birth-weight infants on the 1st day of life for serum and red cell folate levels, the infants were randomly allocated into three groups according to the folic acid supplement dose. Forty-six infants were given 25 mu g/d folic acid, 39 were given 50 mu g/d folic acid, and 44 were given 75 mu g/d folic acid. Folic acid could not be given to 12 infants. Follow-up blood samples were obtained at the end of folic acid supplementation. Maternal samples for red cell and serum folate levels and breast milk folate levels were obtained within the first 48 hours and the samples for measuring breastmilk folate level were obtained on the 3rd day postnatally. The feeding modes of the infants, maternal folic acid intake, and details of neonate intensive care unit course were recorded. Results: The mean birth weight and gestational age of the infants were found as 1788.2 +/- 478.4 g and 33.5 +/- 2.9 weeks, respectively. The mean serum and red cell folate levels on admission were found as 21.2 +/- 12.2 ng/mL and 922.7 +/- 460.7 ng/mL, respectively. The mean maternal serum and red cell folate levels and the mean breast milk folate levels were found as 12.3 +/- 7.5 ng/mL, 845.5 +/- 301.4 ng/mL, and 30.6 +/- 33.0 ng/m, respectively. The breast milk folate levels of mothers who were supplemented with folic acid during pregnancy were significantly higher compared with mothers who were not supplemented with folic acid (p

The endoplasmic reticulum (ER) is related to the various signal routes that are activated in unfolded protein response (UPR). The Grp78, Grp94, CHOP, MTJ1 and HMOX1 genes expressions demonstrate UPR activity. In this study, we investigated the UPR gene expressions in larynx epidermoid carcinoma (HEp2) to which dexamethasone (dex) was applied. HEp2 cells were administered for 48 h with different combinations using 0.1 microM and 1 microM dex, 1 mM phenyl butyric acid (PBA) and 100 ng/ml lipopolysaccharide (LPS). The Grp78, Grp94, CHOP, MTJ1 and HMOX1 genes expression was determined using quantitative RT-PCR. The Grp78, MTJ1 and HMOX1 gene expression increased with the administration of 1 microM dex. CHOP expression, on the other hand, decreased with 0.1 microM dex. When dex was combined with LPS, nearly all gene expressions decreased. The increase in Grp78, Grp94, HMOX1 and MTJ1 gene expression was greater in groups in which dex was administered in combination with PBA than in groups in which dex was administered alone. Dex in low dose (0.1 microM) caused a decrease in CHOP expression in HEp2 cells and an increase in Grp78 expression, in particular. The changes in UPR genes expressions may lead to the extended survival of the cells.

WOS: 000337094900112 PubMed: 24622883 Histone deacetylase (HDAC) inhibitors, such as trichostatin A (TSA), and iron chelators, including deferoxamine (DFO) and phenanthroline (PHEN), appear to have anticancer effects. We hypothesized that the HDAC inhibitors and iron chelators would be synergistic with their effect on breast cancer cell line MCF7, because the HDAC inhibitors increase glucose-regulated protein 78 (Grp78) and the iron chelators reduce its expression. Although the administration of TSA alone resulted in a dose-related decrease in the cell index, it did not have an antiproliferative effect except the 62.5 and 500 nM of TSA. However, all doses of TSA produced a cytotoxic effect from the initial hours when combined with 150 mu M of DFO and 25 mu M of PHEN. DFO and PHEN downregulated Grp78, Grp94, and MRP1 expressions and upregulated CHOP and HO-1 expressions. TSA upregulated all the genes in various rates when used alone but resulted in decreased expression levels when combined with DFO and PHEN. Increased HDAC-1 levels in the Grp78 promoter region indicated that DFO and PHEN either promoted binding of HDAC-1 to this region or inhibited its detachment. We determined that the reduction of increased Grp78, Grp94, HO-1, and MRP1 expressions, which appears to inhibit the chemotherapeutic effect of TSA, through the combination with DFO or PHEN will contribute to the anticancer effect. Ondokuz Mayis UniversityOndokuz Mayis University; [PYO.TIP. 1901 09 001] This study was supported by the Ondokuz Mayis University. The project number was PYO.TIP. 1901 09 001.

AVCI, Bahattin/0000-0001-6471-6495 WOS: 000311201500030 PubMed: 22890828 Our purpose in this study is to analyze mitochondrial DNA (mtDNA) lesion frequencies and mtDNA(4977) deletion in HepG2 cells to examine the effects of ouabain on mtDNA. HepG2 cells were treated with 0.75, 7.5, 75, and 750 nM of ouabain for 24 h in the presence and absence of 10 mM 2-deoxyglucose (2-DG). The frequency of mtDNA(4977) deletions and mitochondrial lesions were determined by real-time polymerase chain reaction. A a parts per thousand yen1.2-fold change or greater was considered significant. Ouabain doses of 750, 75, and 7.5 nM alone increased the frequency of mtDNA(4977) deletions 1.39, 1.92, and 1.44 times, respectively. The 750 and 75 nM ouabain doses combined with 2-DG increased the mtDNA(4977) deletion frequency 4.94 and 1.57 times, respectively. The 750 and 75 nM ouabain doses alone increased the mtDNA lesion frequency 2.5 and 1.5 times, respectively. The 750 nM ouabain dose combined with 2-DG increased the mtDNA lesion frequency 2.28 times. The 7.5 nM ouabain dose alone and combined with 2-DG decreased the mtDNA lesion frequency 0.67 and 0.45 times, respectively. Ouabain alone and when combined with 2-DG increases mtDNA lesion and mtDNA(4977) deletion frequencies. This supports the thesis that ouabain creates oxidative stress and induces DNA damage and apoptosis. Ondokuz Mayis UniversityOndokuz Mayis University This study was supported by Ondokuz Mayis University Research Fund.

WOS: 000309986200001 Glucose regulated protein 78 (Grp78) is a chaperon which acts in the protein folding. Cell-surface Grp78 is present on the surface of different type cancer cells. There are evidences that acetylsalicylic acid (ASA) provides advantages when combined with other chemotherapeutic agents in cancer patients. Resistance is an important problem in cancer treatment and etoposide is a drug which develops resistance against itself. Our purpose in this study is to see how the ASA, either used alone or combined with etoposide, affect on the HepG2 cell viability and to investigate the relationship of this viability with the cell-surface Grp78. Thus 12 different groups were assigned. Control group, 0.5 mu g/ml etoposide group, 2.5, 5, 10 mM ASA groups, 10 mM 2-deoxyglucose (2-DG) + 0.5 mu g/ml etoposide group and the groups added to this group with 2.5, Sand 10 mM ASA respectively, 10 mM 2-DG +2.5 mM ASA group, 10 mM 2-DG + 5 mM ASA group, 10 mM 2-DG + 10 mM ASA group. MIT test was applied for the follow up of the viability of the cells. When the viability in etoposite group was %84.5, the viability in 2-DG+etoposit group was %75.4. This shows that 2-DG decreases the viability of the cells a little. Also, when ASA is applied alone or combined with 2-DG, it caused decrease in the cell viability but this effect was more significant when combined with 2-DG. When etoposide and ASA were combined, the decrease in high-dose viability was more significant. Cell surface Grp78 levels were higher in the group in which 2-DG and ASA were combined each other than the group in which ASA was applied alone. All these results show that cell-surface Grp78 is important for ASA showing its effect. New treatment protocols focused on the cell-surface Grp78 in cancer treatment can be revealed by further studies.

PubMed ID: 22757644, Ouabain is a cardiotonic steroid and specific inhibitor of the Na +/K+-ATPase. The relationship between ouabain treatment and the unfolded protein response (UPR) in cells is not precisely understood. Therefore, we studied the possible effects of ouabain on proliferation, apoptosis, and the UPR. HepG2 cells were cultured overnight and then treated with various concentrations of ouabain (0.75 to 750nM) in the absence or presence of 10mM 2-deoxyglucose (2-DG) for 48 hours. We also used real-time polymerase chain reaction to obtain quantitative measurements of expression levels of Grp78, Grp94, CHOP, MTJ-1, HKII, MDR-1, MRP-1, HO-1, and Par-4. Cell number, viability, and proliferation of HepG2 cells were monitored with a real-time cell analyzer system (xCELLigence). We show that ouabain modulates the UPR transcription program and induces cell death in glucose-deprived tumor cells. Ouabain at all concentrations showed no cytotoxicity whereas all concentrations were very effective under 2-DG stress conditions. Our findings show that disruption of the UPR during glucose deprivation could be an attractive approach for selective cancer cell killing and could provide a chemical basis for developing UPR-targeting drugs against solid tumors. Ouabain use as an adjunct to conventional cancer therapy also warrants vigorous investigation. © Copyright 2012, Mary Ann Liebert, Inc. 2012.