Vitamin C Research Today is a free monthly online journal that collates and summarizes the latest research about Vitamin C, including details on benefits, dosage, supplements, information.

Hexavalent chromium-induced apoptosis of granulosa cells involves selective sub-cellular translocation of Bcl-2 members, ERK1/2 and p53.

Banu SK, Stanley JA, Lee J, Stephen SD, Arosh JA, Hoyer PB, Burghardt RC

Department of Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA. skbanu@cvm.tamu.edu

Hexavalent chromium (CrVI) has been widely used in industries throughout the world. Increased usage of CrVI and atmospheric emission of CrVI from catalytic converters of automobiles, and its improper disposal causes various health hazards including female infertility. Recently we have reported that lactational exposure to CrVI induced a delay/arrest in follicular development at the secondary follicular stage. In order to investigate the underlying mechanism, primary cultures of rat granulosa cells were treated with 10 μM potassium dichromate (CrVI) for 12 and 24h, with or without vitamin C pre-treatment for 24h. The effects of CrVI on intrinsic apoptotic pathway(s) were investigated. Our data indicated that CrVI: (i) induced DNA fragmentation and increased apoptosis, (ii) increased cytochrome c release from the mitochondria to cytosol, (iii) downregulated anti-apoptotic Bcl-2, Bcl-XL, HSP70 and HSP90; upregulated pro-apoptotic BAX and BAD, (iv) altered translocation of Bcl-2, Bcl-XL, BAX, BAD, HSP70 and HSP90 to the mitochondria, (v) upregulated p-ERK and p-JNK, and selectively translocated p-ERK to the mitochondria and nucleus, (vi) activated caspase-3 and PARP, and (vii) increased phosphorylation of p53 at ser-6, ser-9, ser-15, ser-20, ser-37, ser-46 and ser-392, increased p53 transcriptional activation, and downregulated MDM-2. Vitamin C pre-treatment mitigated CrVI effects on apoptosis and related pathways. Our study, for the first time provides a clear insight into the effect of CrVI on multiple pathways that lead to apoptosis of granulosa cells which could be mitigated by vitamin C.

Published 1 March 2011 in Toxicol Appl Pharmacol, 251(3): 253-66.
Full-text of this article is available online (may require subscription).

Articles on Vitamin C published 21 January 2011:

Dietary, but not supplemental, intakes of carotenoids and vitamin C are associated with decreased odds of lower urinary tract symptoms in men.   J Nutr, 141(2): 267-73.

Lower urinary tract symptoms (LUTS) in men may be related to micronutrients involved in prevention of oxidative damage or cell growth and differentiation. We tested the hypothesis that carotenoid, vitamin A, and vitamin C intake were inversely associated with total LUTS, voiding, and storage symptoms. We conducted a cross-sectional multivariate analysis of 1466 men aged 30-79 y in the Boston Area Community Health survey (2002-2005), a population-based random sample survey. Data were collected ... [Abstract] [Full-text]

Dietary ascorbate intake affects steady state tissue concentrations in vitamin C-deficient mice: tissue deficiency after suboptimal intake and superior bioavailability from a food source (kiwifruit).   Am J Clin Nutr, 93(2): 292-301.

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Articles on Vitamin C published 17 January 2011:

Nitric oxide mediates tightening of the endothelial barrier by ascorbic acid.   Biochem Biophys Res Commun, 404(2): 701-5.

Vitamin C, or ascorbic acid, decreases paracellular endothelial permeability in a process that requires rearrangement of the actin cytoskeleton. To define the proximal mechanism of this effect, we tested whether it might involve enhanced generation and/or sparing of nitric oxide (NO) by the vitamin. EA.hy926 endothelial cells cultured on semi-porous filter supports showed decreased endothelial barrier permeability to radiolabeled inulin in response to exogenous NO provided by the NO donor ... [Abstract] [Full-text]

Progressive pseudogenization: vitamin C synthesis and its loss in bats.   Mol Biol Evol, 28(2): 1025-31.

For the past 50 years, it was believed that all bats, like humans and guinea pigs, did not synthesize vitamin C (Vc) because they lacked activity of L-gulonolactone oxidase (GULO) in their livers. Humans and guinea pigs lack the activity due to pseudogenization of GULO in their genomes, but there is no genetic evidence to show whether such loss in bats is caused by pseudogenization. Unexpectedly, our successful molecular cloning in one frugivorous bat (Rousettus leschenaultii) and one ... [Abstract] [Full-text]

Articles on Vitamin C published 5 January 2011:

High dietary fat and cholesterol exacerbates chronic vitamin C deficiency in guinea pigs.   Br J Nutr, 105(1): 54-61.

Vitamin C deficiency - or hypovitaminosis C defined as a plasma concentration below 23 μm - is estimated to affect hundreds of millions of people in the Western world, in particular subpopulations of low socio-economic status that tend to eat diets of poor nutritional value. Recent studies by us have shown that vitamin C deficiency may result in impaired brain development. Thus, the aim of the present study was to investigate if a poor diet high in fat and cholesterol affects the vitamin C ... [Abstract] [Full-text]

Gold kiwifruit consumed with an iron-fortified breakfast cereal meal improves iron status in women with low iron stores: a 16-week randomised controlled trial.   Br J Nutr, 105(1): 101-9.

Ascorbic acid, and more recently, the carotenoids lutein and zeaxanthin have been shown to enhance Fe absorption. However, it is not clear whether Fe status improves when foods high in ascorbic acid and carotenoids are consumed with Fe-fortified meals. The present study aimed to investigate whether consuming high v. low ascorbic acid-, lutein- and zeaxanthin-rich fruit (gold kiwifruit v. banana) with Fe-fortified breakfast cereal and milk improved Fe status in women with low Fe stores. Healthy ... [Abstract] [Full-text]

Articles on Vitamin C published 3 January 2011:

The antioxidant ascorbic acid mobilizes nuclear copper leading to a prooxidant breakage of cellular DNA: implications for chemotherapeutic action against cancer.   Cancer Chemother Pharmacol, 67(1): 103-10.

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Articles on Vitamin C published 24 December 2010:

Selective ascorbate toxicity in malignant mesothelioma: a redox Trojan mechanism.   Am J Respir Cell Mol Biol, 44(1): 108-17.

We studied the mechanism of ascorbate toxicity in malignant mesothelioma (MMe) cells. Neutral red uptake showed that ascorbate, but not dehydroascorbate, was highly toxic in the MMe cell lines REN and MM98, and less toxic in immortalized (human mesothelial cells-htert) and primary mesothelial cells. Ascorbate transport inhibitors phloretin, sodium azide, and ouabain did not reduce ascorbate toxicity. Ascorbate promoted the formation of H(2)O(2) in the cell medium, and its toxicity was ... [Abstract] [Full-text]

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