Skip to main content

Advertisement

SpringerLink
Log in

Protein disulfide isomerase A3 might be involved in the regulation of 24-dehydrocholesterol reductase via vitamin D equilibrium in primary cortical neurons

  • Published:
In Vitro Cellular & Developmental Biology - Animal Aims and scope Submit manuscript

Abstract

Vitamin D is a secosteroid hormone mediating its functions via vitamin D receptor (VDR) and an endoplasmic reticulum chaperone, protein disulfide isomerase A3 (PDIA3). From a physiological perspective, there is also a well-established association of cholesterol and vitamin D synthesis, since both share a common metabolic substrate, 7 dehydrocholesterol (7-DHC). Yet, the potential basic pathways, of the biological interplay of DHCR24 and vitamin D equilibrium, on neuronal level, are yet to be determined. In this study, we aimed to investigate the relation between vitamin D pathways and DHCR24 in primary cortical neuron cultures. The neocortex of Sprague–Dawley rat embryos (E16) was used for the preparation of primary cortical neuron cultures. DHCR24 mRNA and protein expression levels were determined by qRT-PCR, Western blotting, and immunofluorescent labeling in 1,25-dihydroxyvitamin D3-treated or VDR/PDIA3-silenced primary cortical neurons. The mRNA expression of DHCR24 was significantly decreased in the cortical neurons treated with 10-8M 1,25-dihydroxyvitamin D3 (p<0.001). In parallel with the mRNA results, DHCR24 protein expression in cortical neurons treated with 10-8M 1,25-dihydroxyvitamin D3 was also significantly lower than untreated neurons (p<0.05). These data were also confirmed with immunofluorescent labeling and fluorescence intensity measurements of DHCR24 (p<0.001). Finally, DHCR24 mRNA expression level was significantly increased in PDIA3 siRNA-treated neurons (p<0.05). Similar to the mRNA results, the DHCR24 protein expression of PDIA3 siRNA-treated neurons was also statistically higher than the other groups (p<0.05). Results of this mechanistic experimental basic study demonstrate that DHCR24 mRNA expression and protein concentrations attenuated in response to vitamin D treatment. Furthermore, we observed that PDIA3 might be involved in this modulatory effect. Our findings indicate a complex interaction of DHCR24 and vitamin D equilibrium, through the involvement of PDIA3 and vitamin D in the modulation of cholesterol metabolism in neuronal cells, requiring future studies on the field.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1.
Figure 2.
Figure 3.
Figure 4.

Similar content being viewed by others

Data availability

All data generated or analyzed during this study are included in this published article

References

  • Andreu CI, Woehlbier U, Torres M, Hetz C (2012) Protein disulfide isomerases in neurodegeneration: from disease mechanisms to biomedical applications. FEBS Lett 586(18):2826–2834

    Article  CAS  PubMed  Google Scholar 

  • Atasoy IL, Dursun E, Gezen-Ak D, Metin-Armagan D, Ozturk M, Yilmazer S (2017) Both secreted and the cellular levels of BDNF attenuated due to tau hyperphosphorylation in primary cultures of cortical neurons. J Chem Neuroanat 80:19–26

    Article  CAS  PubMed  Google Scholar 

  • Baggerly CA, Cuomo RE, French CB, Garland CF, Gorham ED, Grant WB, Heaney RP, Holick MF, Hollis BW, McDonnell SL, Pittaway M, Seaton P, Wagner CL, Wunsch A (2015) Sunlight and vitamin D: necessary for public health. J Am Coll Nutr 34(4):359–365

    Article  PubMed Central  PubMed  Google Scholar 

  • Bargsted L, Hetz C, Matus S (2016) ERp57 in neurodegeneration and regeneration. Neural Regen Res 11(2):232–233

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Behl C (2002) Estrogen can protect neurons: modes of action. J Steroid Biochem Mol Biol 83(1):195–197

    Article  CAS  PubMed  Google Scholar 

  • Belič A, Pompon D, Monostory K, Kelly D, Kelly S, Rozman D (2013) An algorithm for rapid computational construction of metabolic networks: a cholesterol biosynthesis example. Comput Biol Med 43(5):471–480

    Article  CAS  PubMed  Google Scholar 

  • Benvenuti S, Luciani P, Cellai I, Deledda C, Baglioni S, Saccardi R, Urbani S, Francini F, Squecco R, Giuliani C, Vannelli GB, Serio M, Pinchera A, Peri A (2008) Thyroid hormones promote cell differentiation and up-regulate the expression of the seladin-1 gene in in vitro models of human neuronal precursors. J Endocrinol 197(2):437–446

    Article  CAS  PubMed  Google Scholar 

  • Benvenuti S, Luciani P, Vannelli GB, Gelmini S, Franceschi E, Serio M, Peri A (2005) Estrogen and selective estrogen receptor modulators exert neuroprotective effects and stimulate the expression of selective Alzheimer's disease indicator-1, a recently discovered antiapoptotic gene, in human neuroblast long-term cell cultures. J Clin Endocrinol Metab 90(3):1775–1782

    Article  CAS  PubMed  Google Scholar 

  • Boyan BD, Chen J, Schwartz Z (2012) Mechanism of Pdia3-dependent 1α, 25-dihydroxy vitamin D3 signaling in musculoskeletal cells. Steroids 77(10):892–896

    Article  CAS  PubMed  Google Scholar 

  • Brown AJ, Sun L, Feramisco JD, Brown MS, Goldstein JL (2002) Cholesterol addition to ER membranes alters conformation of SCAP, the SREBP escort protein that regulates cholesterol metabolism. Mol Cell 10(2):237–245

    Article  CAS  PubMed  Google Scholar 

  • Daimiel LA, Fernández-Suárez ME, Rodríguez-Acebes S, Crespo L, Lasunción MA, Gómez-Coronado D, Martínez-Botas J (2013) Promoter analysis of the DHCR24 (3β-hydroxysterol Δ24-reductase) gene: characterization of SREBP (sterol-regulatoryelement-binding protein)-mediated activation. Biosci Rep 33(1):e00006

    Article  CAS  Google Scholar 

  • Dietschy JM (2009) Central nervous system: cholesterol turnover, brain development and neurodegeneration. Biol Chem 390(4):287–293

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Dietschy JM, Turley SD (2004) Thematic review series: brain lipids. Cholesterol metabolism in the central nervous system during early development and in the mature animal. J Lipid Res 45(8):1375–1397

    Article  CAS  PubMed  Google Scholar 

  • Dursun E, Alaylioglu M, Bilgic B, Hanagasi H, Lohmann E, Atasoy IL, Candas E, Araz OS, Onal B, Gurvit H, Yilmazer S, Gezen-Ak D (2016) Vitamin D deficiency might pose a greater risk for ApoEvarepsilon4 non-carrier Alzheimer's disease patients. Neurol Sci 37(10):1633–1643

    Article  PubMed  Google Scholar 

  • Dursun E, Candas E, Yilmazer S, Gezen-Ak D (2019) Amyloid Beta 1-42 alters the expression of miRNAs in cortical neurons. J Mol Neurosci 67(2):181–192

    Article  CAS  PubMed  Google Scholar 

  • Dursun E, Gezen-Ak D (2017) Vitamin D receptor is present on the neuronal plasma membrane and is co-localized with amyloid precursor protein, ADAM10 or Nicastrin. PLoS One 12(11):e0188605

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Dursun E, Gezen-Ak D (2019) Vitamin D basis of Alzheimer's disease: from genetics to biomarkers. Hormones (Athens) 18(1):7–15. https://doi.org/10.1007/s42000-018-0086-5

  • Dursun E, Gezen-Ak D, Yilmazer S (2011) A novel perspective for Alzheimer's disease: vitamin D receptor suppression by amyloid-beta and preventing the amyloid-beta induced alterations by vitamin D in cortical neurons. J Alzheimers Dis 23(2):207–219

    Article  CAS  PubMed  Google Scholar 

  • Dursun E, Gezen-Ak D, Yilmazer S (2013a) Beta amyloid suppresses the expression of the vitamin d receptor gene and induces the expression of the vitamin d catabolic enzyme gene in hippocampal neurons. Dement Geriatr Cogn Disord 36(1-2):76–86

    Article  CAS  PubMed  Google Scholar 

  • Dursun E, Gezen-Ak D, Yilmazer S (2013b) A new mechanism for amyloid-beta induction of iNOS: vitamin D-VDR pathway disruption. J Alzheimers Dis 36(3):459–474

    Article  CAS  PubMed  Google Scholar 

  • Dursun E, Gezen-Ak D, Yilmazer S (2014) The influence of vitamin D treatment on the inducible nitric oxide synthase (INOS) expression in primary hippocampal neurons. Noro Psikiyatr Ars 51(2):163–168

    Article  PubMed Central  PubMed  Google Scholar 

  • Ferraro A, Altieri F, Coppari S, Eufemi M, Chichiarelli S, Turano C (1999) Binding of the protein disulfide isomerase isoform ERp60 to the nuclear matrix-associated regions of DNA. J Cell Biochem 72(4):528–539

    Article  CAS  PubMed  Google Scholar 

  • Fünfschilling U, Saher G, Xiao L, Möbius W, Nave K-A (2007) Survival of adult neurons lacking cholesterol synthesis in vivo. BMC Neurosci 8(1):1

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Garbi N, Tanaka S, Momburg F, Hämmerling GJ (2006) Impaired assembly of the major histocompatibility complex class I peptide-loading complex in mice deficient in the oxidoreductase ERp57. Nat Immunol 7(1):93–102

    Article  CAS  PubMed  Google Scholar 

  • Gezen-Ak D, Alaylioglu M, Genc G, Sengul B, Keskin E, Sordu P, Gulec ZEK, Apaydin H, Bayram-Gurel C, Ulutin T, Yilmazer S, Ertan S, Dursun E (2020) Altered transcriptional profile of mitochondrial DNA-encoded OXPHOS subunits, mitochondria quality control genes, and intracellular ATP levels in blood samples of patients with Parkinson's disease. J Alzheimers Dis 74(1):287–307

    Article  CAS  PubMed  Google Scholar 

  • Gezen-Ak D, Atasoy IL, Candas E, Alaylioglu M, Dursun E (2018) The transcriptional regulatory properties of amyloid beta 1-42 may include regulation of genes related to neurodegeneration. NeuroMolecular Med 20(3):363–375

    Article  CAS  PubMed  Google Scholar 

  • Gezen-Ak D, Atasoy IL, Candas E, Alaylioglu M, Yilmazer S, Dursun E (2017) Vitamin D receptor regulates amyloid beta 1-42 production with protein disulfide isomerase A3. ACS Chem Neurosci 8(10):2335–2346

    Article  CAS  PubMed  Google Scholar 

  • Gezen-Ak D, Dursun E (2019) Molecular basis of vitamin D action in neurodegeneration: the story of a team perspective. Hormones (Athens) 18(1):17–21. https://doi.org/10.1007/s42000-018-0087-4

  • Gezen-Ak D, Dursun E, Yilmazer S (2011) The effects of vitamin D receptor silencing on the expression of LVSCC-A1C and LVSCC-A1D and the release of NGF in cortical neurons. PLoS One 6(3):e17553

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Gezen-Ak D, Dursun E, Yilmazer S (2013a) The effect of vitamin D treatement on nerve growth factor release (NGF) in hippocampal neurons. Arch Neuropsych 51:157–162. https://doi.org/10.4274/npa.y7076

    Article  Google Scholar 

  • Gezen-Ak D, Dursun E, Yilmazer S (2013b) Vitamin D inquiry in hippocampal neurons: consequences of vitamin D-VDR pathway disruption on calcium channel and the vitamin D requirement. Neurol Sci 34(8):1453–1458

    Article  PubMed  Google Scholar 

  • Gezen-Ak D, Yilmazer S, Dursun E (2014) Why vitamin D in Alzheimer's disease? The hypothesis. J Alzheimers Dis 40(2):257–269

    Article  CAS  PubMed  Google Scholar 

  • Giannini S, Benvenuti S, Luciani P, Manuelli C, Cellai I, Deledda C, Pezzatini A, Vannelli GB, Maneschi E, Rotella CM, Serio M, Peri A (2008) Intermittent high glucose concentrations reduce neuronal precursor survival by altering the IGF system: the involvement of the neuroprotective factor DHCR24 (Seladin-1). J Endocrinol 198(3):523–532

    Article  CAS  PubMed  Google Scholar 

  • Greeve I, Hermans-Borgmeyer I, Brellinger C, Kasper D, Gomez-Isla T, Behl C, Levkau B, Nitsch RM (2000) The human DIMINUTO/DWARF1 homolog seladin-1 confers resistance to Alzheimer's disease-associated neurodegeneration and oxidative stress. J Neurosci 20(19):7345–7352

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Guo Y-X, He L-Y, Zhang M, Wang F, Liu F, Peng W-X (2016) 1,25-Dihydroxyvitamin D3 regulates expression of LRP1 and RAGE in vitro and in vivo, enhancing Aβ1–40 brain-to-blood efflux and peripheral uptake transport. Neuroscience 322:28–38

    Article  CAS  PubMed  Google Scholar 

  • Gupta AK, Sexton RC, Rudney H (1989) Effect of vitamin D3 derivatives on cholesterol synthesis and HMG-CoA reductase activity in cultured cells. J Lipid Res 30(3):379–386

    Article  CAS  PubMed  Google Scholar 

  • Hanukoglu I (1992) Steroidogenic enzymes: structure, function, and role in regulation of steroid hormone biosynthesis. J Steroid Biochem Mol Biol 43(8):779–804

    Article  CAS  PubMed  Google Scholar 

  • Henry HL (2011) Regulation of vitamin D metabolism. Best Pract Res Clin Endocrinol Metab 25(4):531–541

    Article  CAS  PubMed  Google Scholar 

  • Herman GE (2003) Disorders of cholesterol biosynthesis: prototypic metabolic malformation syndromes. Hum Mol Genet 12(suppl_1):R75–R88

    Article  CAS  PubMed  Google Scholar 

  • Hetz C, Mollereau B (2014) Disturbance of endoplasmic reticulum proteostasis in neurodegenerative diseases. Nat Rev Neurosci 15(4):233–249

    Article  CAS  PubMed  Google Scholar 

  • Holick MF (2014) Cancer, sunlight and vitamin D. J Clin Transl Endocrinol 1(4):179–186

    PubMed Central  PubMed  Google Scholar 

  • Horton JD, Goldstein JL, Brown MS (2002) SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver. J Clin Invest 109(9):1125–1131

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Horton JD, Shah NA, Warrington JA, Anderson NN, Park SW, Brown MS, Goldstein JL (2003) Combined analysis of oligonucleotide microarray data from transgenic and knockout mice identifies direct SREBP target genes. Proc Natl Acad Sci 100(21):12027–12032

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Horvat S, Mcwhir J, Rozman D (2011) Defects in cholesterol synthesis genes in mouse and in humans: lessons for drug development and safer treatments. Drug Metab Rev 43(1):69–90

    Article  CAS  PubMed  Google Scholar 

  • Incardona JP, Eaton S (2000) Cholesterol in signal transduction. Curr Opin Cell Biol 12(2):193–203

    Article  CAS  PubMed  Google Scholar 

  • Khanal R, Nemere I (2007) The ERp57/GRp58/1, 25D3-MARRS receptor: multiple functional roles in diverse cell systems. Curr Med Chem 14(10):1087–1093

    Article  CAS  PubMed  Google Scholar 

  • Kiourtzidis M, Kuhn J, Brandsch C, Stangl GI (2020) Vitamin D status of mice deficient in scavenger receptor class B type 1, cluster determinant 36 and ATP-binding cassette proteins G5/G8. Nutrients 12(8)

  • Kuehnle K, Crameri A, Kälin RE, Luciani P, Benvenuti S, Peri A, Ratti F, Rodolfo M, Kulic L, Heppner FL (2008) Prosurvival effect of DHCR24/Seladin-1 in acute and chronic responses to oxidative stress. Mol Cell Biol 28(2):539–550

    Article  CAS  PubMed  Google Scholar 

  • Lee JN, Bae SH, Paik YK (2002) Structure and alternative splicing of the rat 7-dehydrocholesterol reductase gene. Biochim Biophys Acta 1576(1-2):148–156

    Article  CAS  PubMed  Google Scholar 

  • Li S, He Y, Lin S, Hao L, Ye Y, Lv L, Sun Z, Fan H, Shi Z, Li J, Feng R, Na L, Wang Y, Li Y, Sun C (2016) Increase of circulating cholesterol in vitamin D deficiency is linked to reduced vitamin D receptor activity via the Insig-2/SREBP-2 pathway. Mol Nutr Food Res 60(4):798–809

    Article  CAS  PubMed  Google Scholar 

  • Lin MT, Beal MF (2006) Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature 443(7113):787–795

    Article  CAS  PubMed  Google Scholar 

  • Lu X, Li Y, Wang W, Chen S, Liu T, Jia D, Quan X, Sun D, Chang AK, Gao B (2014) 3 β-hydroxysteroid-Δ 24 reductase (DHCR24) protects neuronal cells from apoptotic cell death induced by endoplasmic reticulum (ER) stress. PLoS One 9(1):e86753

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Luciani P, Deledda C, Rosati F, Benvenuti S, Cellai I, Dichiara F, Morello M, Vannelli GB, Danza G, Serio M, Peri A (2008) Seladin-1 is a fundamental mediator of the neuroprotective effects of estrogen in human neuroblast long-term cell cultures. Endocrinology 149(9):4256–4266

    Article  CAS  PubMed  Google Scholar 

  • Luu W, Hart-Smith G, Sharpe LJ, Brown AJ (2015) The terminal enzymes of cholesterol synthesis, DHCR24 and DHCR7, interact physically and functionally. J Lipid Res 56(4):888–897

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Lütjohann D (2006) Cholesterol metabolism in the brain: importance of 24S-hydroxylation. Acta Neurol Scand 114(s185):33–42

    Article  Google Scholar 

  • Maggi A, Ciana P, Belcredito S, Vegeto E (2004) Estrogens in the nervous system: mechanisms and nonreproductive functions. Annu Rev Physiol 66:291–313

    Article  CAS  PubMed  Google Scholar 

  • Matus S, Valenzuela V, Medinas DB, Hetz C (2013) ER dysfunction and protein folding stress in ALS. Int J Cell Biol 2013

  • Mauch DH, Nägler K, Schumacher S, Göritz C, Müller E-C, Otto A, Pfrieger FW (2001) CNS synaptogenesis promoted by glia-derived cholesterol. Science 294(5545):1354–1357

    Article  CAS  PubMed  Google Scholar 

  • Mohamed, A., K. Smith and E. P. de Chaves (2015). The mevalonate pathway in Alzheimer’s disease—cholesterol and non-sterol isoprenoids. Alzheimer's Disease-Challenges for the Future, InTech

  • Nemere I (1996) Apparent nonnuclear regulation of intestinal phosphate transport: effects of 1, 25-dihydroxyvitamin D3, 24, 25-dihydroxyvitamin D3, and 25-hydroxyvitamin D3. Endocrinology 137(6):2254–2261

    Article  CAS  PubMed  Google Scholar 

  • Nemere I (2005) The 1, 25D 3-MARRS protein: contribution to steroid stimulated calcium uptake in chicks and rats. Steroids 70(5):455–457

    Article  CAS  PubMed  Google Scholar 

  • Nemere I, Dormanen MC, Hammond MW, Okamura WH, Norman AW (1994) Identification of a specific binding protein for 1 alpha, 25-dihydroxyvitamin D3 in basal-lateral membranes of chick intestinal epithelium and relationship to transcaltachia. J Biol Chem 269(38):23750–23756

    Article  CAS  PubMed  Google Scholar 

  • Norman AW (1998) Sunlight, season, skin pigmentation, vitamin D, and 25-hydroxyvitamin D: integral components of the vitamin D endocrine system. Am J Clin Nutr 67(6):1108–1110

    Article  CAS  PubMed  Google Scholar 

  • Ohvo-Rekilä H, Ramstedt B, Leppimäki P, Slotte JP (2002) Cholesterol interactions with phospholipids in membranes. Prog Lipid Res 41(1):66–97

    Article  PubMed  Google Scholar 

  • Peri A, Serio M (2008) Neuroprotective effects of the Alzheimer's disease-related gene seladin-1. J Mol Endocrinol 41(5):251–261

    Article  CAS  PubMed  Google Scholar 

  • Prabhu AV, Luu W, Sharpe LJ, Brown AJ (2016) Cholesterol-mediated degradation of 7-dehydrocholesterol reductase switches the balance from cholesterol to vitamin D synthesis. J Biol Chem 291(16):8363–8373

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Radhakrishnan A, Goldstein JL, McDonald JG, Brown MS (2008) Switch-like control of SREBP-2 transport triggered by small changes in ER cholesterol: a delicate balance. Cell Metab 8(6):512–521

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Radhakrishnan A, Sun L-P, Kwon HJ, Brown MS, Goldstein JL (2004) Direct binding of cholesterol to the purified membrane region of SCAP: mechanism for a sterol-sensing domain. Mol Cell 15(2):259–268

    Article  CAS  PubMed  Google Scholar 

  • Ramos MC, Sierra S, Ramirez C, Velasco J, Burgos JS (2012) Simvastatin modulates the Alzheimer's disease-related gene seladin-1. J Alzheimers Dis 28(2):297–301

    Article  CAS  PubMed  Google Scholar 

  • Sengul B, Dursun E, Verkhratsky A, Gezen-Ak D (2021) Overexpression of alpha-synuclein reorganises growth factor profile of human astrocytes. Mol Neurobiol 58(1):184–203

    Article  CAS  PubMed  Google Scholar 

  • Soo-Han B, Young-Ki P (1997) Cholesterol biosynthesis from lanosterol: development of a novel assay method and characterization of rat liver microsomal lanosterol Δ24-reductase. Biochem J 326(2):609–616

    Article  Google Scholar 

  • Suzuki S, Kiyosue K, Hazama S, Ogura A, Kashihara M, Hara T, Koshimizu H, Kojima M (2007) Brain-derived neurotrophic factor regulates cholesterol metabolism for synapse development. J Neurosci 27(24):6417–6427

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Torres M, Medinas DB, Matamala JM, Woehlbier U, Cornejo VH, Solda T, Andreu C, Rozas P, Matus S, Muñoz N (2015) The protein-disulfide isomerase ERp57 regulates the steady-state levels of the prion protein. J Biol Chem 290(39):23631–23645

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Turgeon JL, Carr MC, Maki PM, Mendelsohn ME, Wise PM (2006) Complex actions of sex steroids in adipose tissue, the cardiovascular system, and brain: insights from basic science and clinical studies. Endocr Rev 27(6):575–605

    Article  CAS  PubMed  Google Scholar 

  • Wacker M, Holick MF (2013) Sunlight and vitamin D: a global perspective for health. Dermatoendocrinol 5(1):51–108

    Article  PubMed Central  PubMed  Google Scholar 

  • Waterham HR (2006) Defects of cholesterol biosynthesis. FEBS Lett 580(23):5442–5449

    Article  CAS  PubMed  Google Scholar 

  • Waterham HR, Koster J, Romeijn GJ, Hennekam RC, Vreken P, Andersson HC, FitzPatrick DR, Kelley RI, Wanders RJ (2001) Mutations in the 3β-hydroxysterol Δ 24-reductase gene cause desmosterolosis, an autosomal recessive disorder of cholesterol biosynthesis. Am J Hum Genet 69(4):685–694

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Wu C, Miloslavskaya I, Demontis S, Maestro R, Galaktionov K (2004) Regulation of cellular response to oncogenic and oxidative stress by Seladin-1. Nature 432(7017):640–645

    Article  CAS  PubMed  Google Scholar 

  • Yeagle P (1991) Modulation of membrane function by cholesterol. Biochimie 73(10):1303–1310

    Article  CAS  PubMed  Google Scholar 

  • Zerenturk EJ, Sharpe LJ, Ikonen E, Brown AJ (2013) Desmosterol and DHCR24: unexpected new directions for a terminal step in cholesterol synthesis. Prog Lipid Res 52(4):666–680

    Article  CAS  PubMed  Google Scholar 

  • Zhu H, Wang X, Shi H, Su S, Harshfield GA, Gutin B, Snieder H, Dong Y (2013) A genome-wide methylation study of severe vitamin D deficiency in African American adolescents. J Pediatr 162(5):1004–1009 e1001

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The present work was supported by the Research Fund of Istanbul University-Cerrahpasa, Project nos: 51454, 27781, and 26989 and by the Scientific and Technological Research Council of Turkey-TUBITAK, Project nos: 214S586 and 214S585, and by the Turkish Neurological Society. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Institutional review board statement

The Animal Welfare and Ethics Committee of Istanbul University approved the study with the additional protocol number 06. April. 2017-133713 (original protocol number 02. May. 2015-2015/08). All procedures were done following both the guidelines of the Istanbul University and National Research Council’s manual for the care and use of laboratory animals. The research presented in this article complies with the commonly accepted ‘3Rs’.

Author information

Authors and Affiliations

  1. Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey

    Ulaş Yavuz

  2. Brain and Neurodegenerative Disorders Research Laboratory, Department of Medical Biology, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey

    Merve Alaylıoğlu, Büşra Şengül, Duygu Gezen-Ak & Erdinç Dursun

  3. National Scholarship Foundation, Thessaloniki, Greece

    Spyridon N. Karras

  4. Department of Neuroscience, Institute of Neurological Sciences, Istanbul University-Cerrahpasa, Istanbul, Turkey

    Erdinç Dursun

Authors
  1. Ulaş Yavuz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Merve Alaylıoğlu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Büşra Şengül
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Spyridon N. Karras
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Duygu Gezen-Ak
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Erdinç Dursun
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceived and designed the experiments: DGA and ED. Performed the experiments: UY, MA, BS, ED, and DGA. Analyzed the data: ED and DGA. Drafted and revised the manuscript: UY, MA, SK, ED, and DGA. All authors reviewed the manuscript.

Corresponding authors

Correspondence to Duygu Gezen-Ak or Erdinç Dursun.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Additional information

Editor: Tetsuji Okamoto

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yavuz, U., Alaylıoğlu, M., Şengül, B. et al. Protein disulfide isomerase A3 might be involved in the regulation of 24-dehydrocholesterol reductase via vitamin D equilibrium in primary cortical neurons. In Vitro Cell.Dev.Biol.-Animal 57, 704–714 (2021). https://doi.org/10.1007/s11626-021-00602-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11626-021-00602-5

Keywords

Search

Navigation