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http://dx.doi.org/10.13103/JFHS.2016.31.2.113

Effects of Dietary Cholesterol on Male Reproductive Tracts by Regulating PCSK9 Gene  

Lim, Whasun (Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University)
Bae, Hyocheol (Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University)
Song, Gwonhwa (Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University)
Publication Information
Journal of Food Hygiene and Safety / v.31, no.2, 2016 , pp. 113-118 More about this Journal
Abstract
Proprotein convertase subtilisin/kexin type 9 (PCSK9), is a protein mainly secreted by a liver. The PCSK9 plays an important role in low density lipoprotein (LDL) metabolism acting as a repressor of LDL receptor through transportation of the LDLR to the lysosome for degradation. Thus, the PCSK9 inhibitor suppresses PCSK9-regulated degradation of the LDL receptor as a LDL-lowering medicine. However, little is known about the role of PCSK9 in the reproductive system. Therefore, in the present study, we investigated Pcsk9 expression in male reproductive tracts including penises, prostates and testes using rats in response to their diets between a normal diet and a high-fat diet with cholesterol. Based on our previous study, the high-fat diet elevates concentration of total cholesterol and LDL in serum whereas it reduces the concentration of plasma high density lipoprotein (HDL). In addition, it dramatically affects to morphological changes of the male reproductive organs. Consistent with these results, the expression of Pcsk9 was substantially decreased in the penile tissues (P < 0.001) from rats fed a high fat diet as compared to a normal diet. Moreover, it slightly reduced in the prostate and testes (P < 0.05) of rats in response to a high fat diet. Localization of Pcsk9 was predominantly detected in urethral epithelium of penises, cylinder-shaped cells of prostate glands, and spermatogonia, spermatocytes and spermatid of testes of rats. Collectively, results of current study provide invaluable insights into the Pcsk9 gene with respect to its tissue- and cell-specific expression by a high fat diet with cholesterol.
Keywords
Pcsk9; Cholesterol; Male reproductive tracts; Rat;
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1 V, Charlton-Menys., P, N, Durrington.: Human cholesterol metabolism and therapeutic molecules. Experimental physiology, 93, 27-42 (2008).   DOI
2 Charlton, M.: Obesity, hyperlipidemia, and metabolic syndrome. Liver transplantation, 15, S83-89 (2009).   DOI
3 Jones, P. J.: Dietary cholesterol and the risk of cardiovascular disease in patients: a review of the Harvard Egg Study and other data. International journal of clinical practice, 63, 1-8 (2009).
4 McNamara, D. J.: Dietary cholesterol and atherosclerosis. Biochimica et biophysica acta, 1529, 310-320 (2000).   DOI
5 Puglielli, L., Tanzi, R. E. and Kovacs, D. M.: Alzheimer's disease: the cholesterol connection. Nature neuroscience, 6, 345-351 (2003).   DOI
6 Hu, J., La, Vecchia, C., de, Groh, M., Negri, E., Morrison, H., Mery, L.: Dietary cholesterol intake and cancer. Annals of oncology, 23, 491-500 (2012).   DOI
7 Gupta R, S., Dixit V, P.: Effect of dietary cholesterol on spermatogenesis. Zeitschrift fur Ernahrungswissenschaft, 27, 236-243 (1988).   DOI
8 Lim W., Bae H., Sohn J.Y., Jeong W., Kim S.H., Song G.: Dietary cholesterol affects expression of prostatic acid phosphatase in reproductive organs of male rats. Biochemical and biophysical research communications, 456, 421-427, (2015).   DOI
9 Miner, M., Billups, K, L.: Erectile dysfunction and dyslipidemia: relevance and role of phosphodiesterase type-5 inhibitors and statins. The journal of sexual medicine, 5, 1066-1078 (2008).
10 Zhang, D, W., Garuti, R., Tang, W, J., Cohen, J, C., Hobbs, H, H.: Structural requirements for PCSK9-mediated degradation of the low-density lipoprotein receptor. Proc Natl Acad Sci U S A, 105, 13045-13050 (2008).   DOI
11 Brown, M, S., Goldstein, J, L.: The SREBP pathway: regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor. Cell, 89, 331-340 (1997).   DOI
12 Abifadel, M., Varret, M., Rabès, JP., Allard, D., Ouguerram, K., Devillers, M., Cruaud, C., Benjannet, S., Wickham, L., Erlich, D., Derré, A., Villéger, L., Farnier, M., Beucler, I., Bruckert, E., Chambaz, J., Chanu, B., Lecerf, JM., Luc, G., Moulin, P., Weissenbach, J., Prat, A., Krempf, M., Junien, C., Seidah, NG., Boileau, C.: Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nature genetics, 34, 154-156 (2003).   DOI
13 Kim S.C.: Hyperlipidemia and erectile dysfunction. Asian journal of andrology, 2, 161-166 (2000).
14 Musicki, B., Liu, T., Lagoda, G,A., Strong, T,D., Sezen, S,F., Johnson, J,M., Burnett, A,L.: Hypercholesterolemia-induced erectile dysfunction: endothelial nitric oxide synthase (eNOS) uncoupling in the mouse penis by NAD(P)H oxidase. The journal of sexual medicine, 7, 3023-3032 (2010).   DOI
15 Kim J.H., Klyachkin, M,L., Svendsen, E., Davies, M,G., Hagen, P,O., Carson, C,C.: Experimental hypercholesterolemia in rabbits induces cavernosal atherosclerosis with endothelial and smooth muscle cell dysfunction. The Journal of urology, 151, 198-205 (1994).   DOI
16 Ahn J., Lim U., Weinstein, S,J., Schatzkin, A., Hayes, R,B., Virtamo, J., Albanes, D.: Prediagnostic total and high-density lipoprotein cholesterol and risk of cancer. Cancer epidemiology, biomarkers & prevention, 18, 2814-2821 (2009).   DOI
17 Mondul, A, M., Clipp, S, L., Helzlsouer, K, J., Platz, E, A.: Association between plasma total cholesterol concentration and incident prostate cancer in the CLUE II cohort. Cancer Cause Control, 21, 61-68 (2010).   DOI
18 Zhuang, L., Kim, J., Adam, R, M., Solomon, K, R., Freeman, M, R.: Cholesterol targeting alters lipid raft composition and cell survival in prostate cancer cells and xenografts. The Journal of clinical investigation, 115, 959-968 (2005).   DOI
19 Freeman, M, R., Solomon, K, R.: Cholesterol and benign prostate disease. Differentiation, 82, 244-252 (2011).   DOI
20 Martinez-Martos, JM., Arrazola, M., Mayas, M,D., Carrera-Gonzalez, M,P., Garcia, M,J., Ramírez-Exposito, M,J.: Dietinduced hypercholesterolemia impaired testicular steroidogenesis in mice through the renin-angiotensin system. Gen Comp Endocrinol, 173, 15-19 (2011).   DOI
21 Diaz-Fontdevila, M., Bustos-Obregon, E.: Cholesterol and polyunsaturated acid enriched diet: effect on kinetics of the acrosome reaction in rabbit spermatozoa. Molecular reproduction and development, 35, 176-180 (1993).   DOI