$\require{mediawiki-texvc}$
  • 검색어에 아래의 연산자를 사용하시면 더 정확한 검색결과를 얻을 수 있습니다.
  • 검색연산자
검색연산자 기능 검색시 예
() 우선순위가 가장 높은 연산자 예1) (나노 (기계 | machine))
공백 두 개의 검색어(식)을 모두 포함하고 있는 문서 검색 예1) (나노 기계)
예2) 나노 장영실
| 두 개의 검색어(식) 중 하나 이상 포함하고 있는 문서 검색 예1) (줄기세포 | 면역)
예2) 줄기세포 | 장영실
! NOT 이후에 있는 검색어가 포함된 문서는 제외 예1) (황금 !백금)
예2) !image
* 검색어의 *란에 0개 이상의 임의의 문자가 포함된 문서 검색 예) semi*
"" 따옴표 내의 구문과 완전히 일치하는 문서만 검색 예) "Transform and Quantization"
쳇봇 이모티콘
안녕하세요!
ScienceON 챗봇입니다.
궁금한 것은 저에게 물어봐주세요.

논문 상세정보

엽산과 비타민 $B_{12}$ 결핍에 의한 호모시스테인혈증 흰쥐의 조직내 비타민 지표간의 상관관계 분석

A Critical Evaluation of the Correlation Between Biomarkers of Folate and Vitamin $B_{12}$ in Nutritional Homocysteinemia

초록

본 연구는 흰쥐를 대상으로 엽산결핍 또는 엽산결핍/비타민 $B_{12}$결핍/0.3% 호모시스틴 식이의 공급을 통해 각각 경미한 호모시스테인혈증과 중위의 호모시스테인혈증을 유도한 후, 혈장, 간 및 뇌 조직내 메티오닌 대사회로 biomarker와 엽산 농도 사이의 상관관계를 분석함으로써 영양성 호모시스테인혈증의 특성을 규명할 목적으로 실시하였다. 6 주령 Sprague-Dawley 숫컷 쥐에게 엽산이 충분한 식이 (FS), 엽산결핍식이 (FD), 또는 동일 식이에 호모시스틴을 첨가한 식이 (FSH and FDH), 엽산결핍/비타민 $B_{12}$ 결핍/호모시스틴 첨가 식이 (FDHCD)를 8주간 공급하였다. 1) FD와 FDH 식이군은 경미한 호모시스테인혈증을 (17.41 ${\pm}$ 1.94 nmol/mL) 나타냈으며, FDHCD 식이군은 중위의 호모시스테인혈증을 (44.13 ${\pm}$ 2.65 nmol/mL) 나타내어 엽산과 비타민 $B_{12}$결핍에 의한 영양성 호모시스테인혈증의 모델로 이용할 수 있었다. 2) FD, FDH, FDHCD 식이군의 간 (p < 0.001)과 뇌조직 (p < 0.01) 내 엽산 농도는 FS, FSH군 보다 유의적으로 낮았으나, FD, FDH, FDHCD 식이군의 간 및 뇌조직의 엽산농도 사이에는 유의적인 차이가 없었다. 이와 대조적으로 혈장 엽산 농도는 FDHCD 식이군 (126.5 ${\pm}$ 9.6 nmol/L)이 FD, FDH 식이군 (21.1 ${\pm}$ 1.4 nmol/L, 22.0 ${\pm}$ 2.2 nmol/L)(p < 0.001) 보다 약 6배 높았으며, 이는 비타민 $B_{12}$ 결핍에 의한"methyl-folate trap"으로 인해 엽산이 효율적으로 조직내 보유되지 못하고 혈류로 나와 소변을 통해 배설되기 때문인 것으로 보인다. 3) FD와 FDH 식이군의 간조직의 SAH 농도는 각각 대조군 보다 44% 및 50%씩 증가되었고 (p < 0.001), 간 SAM 농도는 각각 대조군 보다 72%, 71% 저하되었으며 (p < 0.001), 그 결과 두 군 모두 SAM/SAH 비율이 대조군 보다 약 80% 저하되었다 (p < 0.001). 한편 FDHCD 식 이군의 간 SAH 농도를 대조군과 비교할 때 대조군 보다 107% 증가되었고 (p < 0.001), SAM 농도는 대조군 보다 81% 저하되었으며 (p < 0.001), 그 결과 SAM/SAH 비율이 대조군 보다 약 90% 저하되어 매우 낮은 SAM/SAH 비율을 나타냈다 (p < 0.001). 뇌조직 SAM 농도는 엽산결핍, 비타민 $B_{12}$결핍 및 호모시스틴 급여에 의해 영향을 받지 않고 대조군과 유사한 수준을 보여 뇌조직내 SAM의 항상성을 나타냈으나, FDHCD 식이군의 뇌조직 SAH 농도는 대조군 보다 60% 증가되었으며 (p < 0.05), 그 결과 SAM/SAH 비율은 대조군 보다 약 28% 저하되었다 (p < 0.05). 따라서 중위의 호모시스테인혈증을 나타낸 실험군에서만 뇌조직의 SAH 농도가 증가되었다. 4) 영양결핍 (엽산 또는 비타민 $B_{12}$)에 의한 호모시스테인혈증의 특성을 조사할 목적으로 혈장, 간 및 뇌 조직내 메티오닌 대사회로 biomarker와 엽산 농도 사이의 상관관계를 조사하였다. 혈장 호모시스테인은 간 엽산과 음의 상관관계 (r = -0.641, p < 0.01)을 보였으나, 뇌 엽산 또는 혈장 엽산과는 유의적인 상관관계를 보이지 않았다. 그러나 이와 대조적으로 FDHCD 식이군을 제외시킨 나머지 네개의 실험군 자료만으로 상관관계를 분석하였을 때 혈장 호모시스테인과 뇌 엽산 (r = -0.321, p < 0.05), 혈장 엽산 (r = -0.581, p < 0.01), 간 엽산 (r = -0.684, p < 0.01) 사이에 모두 유의적인 상관관계를 나타냈다. 혈장 호모시스테인과 간조직의 SAH 및 SAM 농도 사이의 상관관계는 FDHCD군을 제외시킨 나머지 네개의 실험군 자료만으로 상관관계를 분석하였을 때 뇌조직 SAH 농도들 제외한 모든 상

Abstract

Folate and vitamin $B_{12}$ are essential cofactors for homocysteine (Hcy) metabolism. Homocysteinemia has been related with cardiovascular and neurodegenerative disease. We examined the effect of folate and/or vitamin $B_{12}$ deficiency on biomarkers of one carbon metabolism in blood, liver and brain, and analyzed the correlation between vitamin biomarkers in mild and moderate homocysteinemia. In this study, Sprague-Dawley male rats (5 groups, n = 10) were fed folatesufficient diet (FS), folate-deficient diet (FD) with 0 or 3 g homocystine (FSH and FDH), and folate-/vitamin $B_{12}$-deficient diet with 3 g homocystine (FDHCD) for 8 weeks. The FDH diet induced mild homocysteinemia (plasma Hcy 17.41 ${\pm}$ 1.94 nmol/mL) and the FDHCD diet induced moderate homocysteinemia (plasma Hcy 44.13 ${\pm}$ 2.65 nmol/mL), respectively. Although liver and brain folate levels were significantly lower compared with those values of rats fed FS or FSH (p < 0.001, p < 0.01 respectively), there were no significant differences in folate levels in liver and brain among the rats fed FD, FDH and FDHCD diet. However, rats fed FDHCD showed higher plasma folate levels (126.5 ${\pm}$ 9.6 nmol/L) compared with rats fed FD and FDH (21.1 ${\pm}$ 1.4 nmol/L, 22.0 ${\pm}$ 2.2 nmol/L)(p < 0.001), which is the feature of "ethyl-folate trap"by vitamin $B_{12}$ deficiency. Plasma Hcy was correlated with hepatic folate (r = -0.641, p < 0.01) but not with plasma folate or brain folate in this experimental condition. However, as we eliminated FDHCD group during correlation test, plasma Hcy was correlated with plasma folate (r = -0.581, p < 0.01), hepatic folate (r = -0.684, p < 0.01) and brain folate (r = -0.321, p < 0.05). Hepatic S-adenosylmethionine (SAM) level was lower in rats fed FD, FDH and FDHCD than in rats fed FS and FSH (p < 0.001, p < 0.001 respectively) and hepatic S-adenosylhomocysteine (SAH) level was significantly higher in those groups. The SAH level in brain was also significantly increased in rats fed FDHCD (p < 0.05). However, brain SAM level was not affected by folate and/or vitamin $B_{12}$ deficiency. This result suggests that dietary folate- and vitamin B12-deficiency may inhibit methylation in brain by increasing SAH rather than decreasing SAM level, which may be closely associated with impaired cognitive function in nutritional homocysteinemia.

저자의 다른 논문

참고문헌 (50)

  1. Selhub J. Public health significance of elevated homocysteine. Food Nutr Bull 2008; 29(2 Suppl): 116-125 
  2. Yap S, Naughten E. Homocystinuria due to cystathionine betasynthase deficiency in Ireland: 25 years’ experience of a newborn screened and treated population with reference to clinical outcome and biochemical control. J Inherit Metab Dis 1998; 21(7): 738-747 
  3. Clarke R, Smith AD, Jobst KA, Refsum H, Sutton L, Ueland PM. Folate, vitamin B12, and serum total homocysteine levels in confirmed Alzheimer disease. Arch Neurol 1998; 55(11): 1449-1455 
  4. Goodwin JS, Goodwin JM, Garry PJ. Association between nutritional status and cognitive functioning in a healthy elderly population. JAMA 1983; 249(21): 2917-2921 
  5. Afman LA, Blom HJ, Drittij MJ, Brouns MR, van Straaten HW. Inhibition of transmethylation disturbs neurulation in chick embryos. Brain Res Dev Brain Res 2005; 158(1-2): 59-65 
  6. Schatz RA, Wilens TE, Sellinger OZ. Decreased transmethylation of biogenic amines after in vivo elevation of brain S-adenosyll-homocysteine. J Neurochem 1981; 36(5): 1739-1748 
  7. Scott JM. Folate-vitamin B12 interrelationships in the central nervous system. Proc Nutr Soc 1992; 51(2): 219-224 
  8. Shane B, Stokstad EL. Vitamin B12-folate interrelationships. Annu Rev Nutr 1985; 5: 115-141 
  9. Tamura T. Microbiological assay of folate, in Folic Acid Metabolism in Health and Disease (Picciano MF, Stokstad ELR, Gregory JF eds.), New York: Wiley-Liss; 1990. p.121-137 
  10. Araki A, Sako Y. Determination of free and total homocysteine in human plasma by HPLC with fluorescence detection. J Chromatogr 1987; 422: 43-52 
  11. Min H, Im ES, Seo JS, Mun JA, Burri BJ. Effects of chronic ethanol ingestion and folate deficiency on the activity of 10-formyltetrahydrofolate dehydrogenase in rat liver. Alcohol Clin Exp Res 2005; 29(12): 2188-2193 
  12. Kutzbach C, Stokstad EL. Mammalian methylenetetrahydrofolate reductase. Partial purification, properties, and inhibition by S-adenosylmethionine. Biochim Biophys Acta 1971; 250(3): 459-477 
  13. Kim YI. Folate and DNA methylation: a mechanistic link between folate deficiency and colorectal cancer? Cancer Epidemiol Biomarkers Prev 2004; 13(4): 511-519 
  14. Eto K, Asada T, Arima K, Makifuchi T, Kimura H. Brain hydrogen sulfide is severely decreased in Alzheimer’s disease. Biochem Biophys Res Commu 2002; 293(5): 1485-1488 
  15. Watkins D, Rosenblatt DS. Functional methionine synthase deficiency (cblE and cblG): clinical and biochemical heterogeneity. Am J Med Genet 1989; 34(3): 427-434 
  16. Lipton SA, Kim WK, Choi YB, Kumar S, D’Emilia DM, Rayudu PV, Arnelle DR, Stamler JS. Neurotoxicity associated with dual actions of homocysteine at the N-methyl-D-aspartate receptor. Proc Natl Acad Sci USA 1997; 94(11): 5923-5928 
  17. Morris MS, Jacques PF, Rosenberg IH, Selhub J. Elevated serum methylmalonic acid concentrations are common among elderly Americans. J Nutr 2002; 132(9): 2799-2803 
  18. Rossi A, Cerone R, Biancheri R, Gatti R, Schiaffino MC, Fonda C, Zammarchi E, Tortori-Donati P. Early-onset combined methylmalonic aciduria and homocystinuria: neuroradiologic findings. Am J Neuroradiol 2001; 22(3): 554-563 
  19. Deacon R, Lumb M, Perry J, Chanarin I, Minty B, Halsey MJ, Nunn JF. Selective inactivation of vitamin B12 in rats by nitrous oxide. Lancet 1978; 2(8098): 1023-1024 
  20. Bird OD, McGlohon VM, Vaitkus JW. A microbiological assay system for naturally occurring folate. Can J Microbio 1969; 15 (5): 465-472 
  21. Riggs KM, Spiro A III, Tucker K, Rush D. Relations of vitamin B-12, vitamin B-6, folate, and homocysteine to cognitive performance in the Normative Aging Study. Am J Clin Nutr 1996; 63(3): 306-314 
  22. Selhub J, Bagley LC, Miller J, Rosenberg IH. B vitamins, homocysteine, and neurocognitive function in the elderly. Am J Clin Nutr 2000; 71(2): 614s-620s 
  23. Mudd SH, Skovby F, Levy HL, Pettigrew KD, Wilcken B, Pyeritz RE, Andria G, Boers GH, Bromberg IL, Cerone R. The natural history of homocystinuria due to cystathionine beta-synthase deficiency. Am J Hum Genet 1985; 37(1): 1-31 
  24. Wagner J, Claverie N, Danzin C. A rapid high-perfornance liquid chromatographic procedure for the simultaneous determination of methionine, ethionine, S-adenosylmethione, S-adenosylethione, and the natural polyamines in rat tissues. Anal Biochem 1984; 140(1): 108-116 
  25. Wong DL, Yamasaki L, Ciaranello RD. Characterization of the isozymes of bovine adrenal medullary phenylethanolamine Nmethyltransferase. Brain Res 1987; 410(1): 32-44 
  26. Fratiglioni L, Ahlbom A, Viitanen M, Winblad B. Risk factors for late-onset Alzheimer’s disease a population-based, case-control study. Ann Neurol 1993; 33(3): 258-266 
  27. Niculescu MD, Zeisel SH. Diet, methyl donors and DNA methylation: interactions between dietary folate, methionine and choline. J Nutr 2002; 132(8 Suppl): 2333s-2335s 
  28. Kim JM, Lee HY, Jang N. Effects of dietary folate supplementation on the homocystine diet-induced hyperhomocysteinemia and hepatic S-adenosylmethionine metabolism in rats. Korean J Nutr 2003; 36(8): 811-818 
  29. Obeid R, Schorr H, Eckert R, Herrmann W. Vitamin B12 status in the elderly as judged by available biochemical markers. Clin Chem 2004; 50(1): 238-241 
  30. Refsum H, Ueland PM, Nygard O, Vollset SE. Homocysteine and cardiovascular disease. Annu Rev Med 1998; 49: 31-62 
  31. Selhub J, Miller JW. The pathogenesis of homocysteinemia: interruption of the coordinate regulation by S-adenosylmethionine of the remethylation and transsulfuration of homocysteine. Am J Clin Nutr 1992; 55(1): 131-138 
  32. Kruman II, Culmsee C, Chan SL, Kruman Y, Guo Z, Penix L, Mattson MP. Homocysteine elicits a DNA damage response in neurons that promotes apoptosis and hypersensitivity to excitotoxicity. J Neurosci 2000; 20(18): 6920-6926 
  33. Penninx BW, Guralnik JM, Ferrucci L, Fried LP, Allen RH, Stabler SP. Vitamin B(12) deficiency and depression in physically disabled older women: epidemiologic evidence from the Women's Health and Aging Study. Am J Psychiatry 2000; 157 (5): 715-721 
  34. Carney MW, Sheffield BF. Serum folic acid and B12 in 272 psychiatric in-patients. Psychol Med 1978; 8(1): 139-144 
  35. Guo Z, Cupples LA, Kurz A, Auerbach SH, Volicer L, Chui H, Green RC, Sadovnick AD, Duara R, DeCarli C, Johnson K, Go RC, Growdon JH, Haines JL, Kukull WA, Farrer LA. Head injury and the risk of AD in the MIRAGE study. Neurology 2000; 54(6): 1316-1323 
  36. Zhu BT, Patel UK, Cai MX, Conney AH. O-Methylation of tea polyphenols catalyzed by human placental cytosolic catechol-Omethyltransferase. Drug Metab Dispos 2000; 28(9): 1024-1030 
  37. Herbert V, Zalusky R. Interrelations of vitamin B12 and folic acid metabolism: folic acid clearance studies. J Clin Invest 1962; 41: 1263-1276 
  38. Kutzbach C, Stokstad EL. Feedback inhibition of methylenetetrahydrofolate reductase in rat liver by S-adenosylmethionine. Biochim Biophys Acta 1967; 139(1): 217-220 
  39. Scott JM, Weir DG. The methyl folate trap. A physiological response in man to prevent methyl group deficiency in kwashiorkor (methionine deficiency) and an explanation for folic-acid induced exacerbation of subacute combined degeneration in pernicious anaemia. Lancet 1981; 2(8242): 337-340 
  40. Hoffman DR, Cornatzer WE, Duerre JA. Relationship between tissue levels of S-adenosylmethionine, S-adenylhomocysteine, and transmethylation reactions. Can J Biochem 1979; 57(1): 56-65 
  41. Kerins DM, Koury MJ, Capdevila A, Rana S, Wagner C. Plasma S-adenosylhomocysteine is a more sensitive indicator of cardiovascular disease than plasma homocysteine. Am J Clin Nutr 2001; 74(6): 723-729 
  42. Carney MW, Chary TK, Laundy M, Bottiglieri T, Chanarin I, Reynolds EH, Toone B. Red cell folate concentrations in psychiatric patients. J Affect Disord 1990; 19(3): 207-213 
  43. Goodwin JS, Goodwin JM, Garry PJ. Association between nutritional status and cognitive functioning in a healthy elderly population. JAMA 1983; 249(21): 2917-2921 
  44. Lee HS, Schulz AR, Fuller RW. Isolation and purification of rabbit adrenal norephinephrine N-methyl transferase isozymes. Arch Biochem Biophys 1978; 185(1): 222-227 
  45. Yi P, Melnyk S, Pogribna M, Pogribny IP, Hine RJ, James SJ. Increase in plasma homocysteine associated with parallel increases in plasma S-adenosylhomocysteine and lymphocyte DNA hypomethylation. J Biol Chem 2000; 275(38): 29318-29323 
  46. Abou-Saleh MT, Coppen A. The biology of folate in depression: implications for nutritional hypotheses of the psychoses. J Psychiatr Res 1986; 20(2): 91-101 
  47. Kim YI, Pogribny IP, Basnakian AG, Miller JW, Selhub J, James SJ, Mason JB. Folate deficiency in rats induces DNA strand breaks and hypomethylation within the p53 tumor suppressor gene. Am J Clin Nutr 1997; 65(1): 46-52 
  48. Seshadri S, Drachman DA, Lippa CF. Apolipoprotein E4 allele and the lifetime risk of Alzheimer's disease. Arch Neurol 1995; 52(11): 1074-1079 
  49. Morris MS. Homocysteine and Alzheimer’s disease. Lancet Neurol 2003; 2(7): 425-428 
  50. Isobe C, Murata T, Sato C, Terayama Y. Increase of total homocysteine concentration in cerebrospinal fluid in patients with Alzheimer’s disease and Parkinson’s disease. Life Sci 2005; 77 (15): 1836-1843 

이 논문을 인용한 문헌 (0)

  1. 이 논문을 인용한 문헌 없음

DOI 인용 스타일