• Investigative Magnetic Resonance Imaging
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• 제3권1호
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• pp.47-52
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• 1999

목적 : 시각자극을 이용하여 대뇌 후두엽에서 BOLD(blood oxygen level dependent)효과에 의한 기능적 자기공명영상과 양성자 자기공명분광법을 이용한 대사물질영상( metabolic i image)을 얻어 그 결과를 평가하고자 하였다. 대상 및 방법 : 24세에서 30세 사이의 8명의 남자와 2명의 여자를 포함하는 10명의 정상 성인 남녀를 대상으로 1.5T MRI에서 시각 지극을 이용하여 echo planar imaging펠스시퀀스를 사용하여 BOLD효과에 의한 영상들을 대뇌 후두엽에서 얻었다. 시각자극은 8Hz의 red flicker를 이용한 광 자극을 주였다. MR에서 얻어진 영상들을 workstation으로 전송한 뒤 자체 개발한 분석프로그램을 사용하여 상관계수방법을 이용하여 기능적 영상을 구하였다. 그리고 얻어진 영상의 활성화 부위를 선정한 뒤 양성자 자기공명 분광법을 사용하여 시각 자극에 의한 뇌 활성화시 대사물질의 변화를 분석했다. 그 후 자가공명분광영상법(magnetic resonance spectro-scopic imaging)를 실행하여 젖산(lactate)의 대사물질 영상을 얻었다. 결과 : 시각 자극에 따른 BOLD효과에 의한 뚜렷한 활성화 부위가 후두염 대뇌피질에 나타났다. 또한 이들 활성화 부위에서 자기공명분광법을 시행한 결과 휴식상태와 시각자극상태에서 NAA(N-acetyle aspartate)/Cr(creatine)이 $1.79{\pm}0.28$에서 $1.88{\pm}O.20$으로 거의 변화가 없는 것에 반해 lactate는 자극 전후 $9.48{\pm}4.38$배로 증가하였으며 이를 바탕으로 lactate에 대한 대사물질영상을 얻을 수 있었다. 결론 : 시각자극에 의한 뇌 활성화시 BOLD효과를 이용한 자기공명영상볍으로 활성화 부위를 확인할 수 있었고, 같은 부위에서 자기공명분광법을 이용하여 lactate의 증가를 확인하였다. 또한 lactate의 증가를 대사물질영상으로 표현함으로써 두 결과에 대한 상관관계 및 뇌 기능적영상에 대한 신뢰성을 높일 수 있게 되었다.

• 대한유전성대사질환학회지
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• 제16권2호
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• pp.109-114
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• 2016

Carbamoyl phosphate synthetase 1 (CPS1) 결핍은 상염색체 열성 유전을 하는 매우 드문 유전질환으로, 요소 회로의 첫 번째 효소인 carbamoyl phosphate synthetase의 결핍에 의해 고암모니아혈증을 유발한다. CPS1 결핍은 신생아시기부터 성인까지 다양한 시기에 고암모니아혈증이 발현될 수 있으나 대부분 신생아 시기의 치명적인 고암모니아혈증으로 발현하여 예후가 불량하며 응급 투석 및 집중 치료가 필요하다. 본 증례는 드문 유전 질환인 CPS1 결핍 신생아에서 새로운 CPS1 유전자의 돌연변이를 발견하였고 조직적인 팀 접근을 통해 심각한 고암모니아혈증에 대한 신속한 투석 및 집중 치료를 시행하여 심한 뇌 병변 및 사망을 예방하고 양호한 경과를 보였음을 보고하는 바이다.

• 한국자기공명학회논문지
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• 제5권2호
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• pp.99-109
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• 2001

Authors investigated neuronal changes of local cellular metabolism in the cerebral lesions of Parkinsonian symptomatic side between before and after stereotactic neurosurgery by follow-up 1H magnetic resonance spectroscopy (MRS). Patients with Parkinson's disease (PD) (n = 15) and age-matched normal controls (n = 15) underwen MRS examinations using a stimulated echo acquisition mode (STEAM) pulse sequence that provided 2${\times}$2${\times}$2 ㎤ (8ml) volume of interest in the regions of substantia nigra, thalamus, and lentiform nucleus. Spectral parameters were 20 ms TE, 2000 ms TR, 128 averages,2500 Hz spectral width, and 2048 data points. Raw data were processed by the SAGE data analysis package (GE Medical Systems). Peak areas of N-acetylaspartate (NAA), creatine (Cr), choline-containing compounds (Cho), inositols (Ins), and the sum (Glx) of glutamate and GABA were calculated by means of fitting the spectrum to a summation of Lorentzian curves using Marquardt algorithm. After blindly processed, we evaluated neuronal alterations of observable metabolite ratios between before and after stereotactic neurosurgery using Pearson product-moment analysis (SPSS, Ver. 6.0). A significant reduction of NAA/Cho ratio was observed in the cerebral lesion in substantia nigra of PD patient related to the symptomatic side after neurosurgery (P : 0.03). In thalamus, NAA/Cho ratio was also significantly decreased in the cerebral lesion including the electrode-surgical region (P : 0.03). A significant reduction of NAA/Cho ratio in lentiform nucleus was not oberved, but tended toward significant reduction after neurosurgery (P = 0.08). In particular, remarkable lactate signal was noted from the surgical thalamic lesions of 6 among 8 patients and internal segments of globus pallidus of 6 among 7 patients, respectively. Significant metabolic alterations of NAA/Cho ratio might reflect functional changes of neuropathological processes in the lesion of substantia nigra, thalamus, and lentiform nucleus, and could be a valuable finding fur evaluation of Parkinson's disease after neurosurgery. Increase of lactate signals, being remarkable in surgical lesions, could be consistent with a common consequence of neurosurgical necrosis. Thus, IH MRS could be a useful modality to evaluate the diagnostic and prognostic implications fur Parkinsons disease after functional neurosurgery.

• 대한유전성대사질환학회지
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• 제14권2호
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• pp.195-199
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• 2014

X 연관 부신백질이영양증(adrenoleukodystrophy, X-ALD)는 성염색체 Xq28에 위치한 ABCD1 유전자의 돌연변이에 의해 발생하며, 매우 긴 사슬 지방산(saturated very long chain fatty acids, VLCFA) 운반의 장애로 뇌와 척수의 백질과 부신 피질을 포함한 모든 조직에 VLCFA가 쌓이게 되어 중추와 말초 신경 조직 내에 탈수초(demyelination)가 진행되고, 부신 피질의 기능 저하가 나타나게 된다. X-ALD의 임상적 증상은 매우 다양하나, 크게 3가지 표현형으로 나누어 대뇌 부신백질형성 장애(cerebral ALD), 부신 척수 신경병증(adrenomyeloneuropathy), 부신 피질 기능 저하 즉 애디슨병(Addison's disease only ALD)으로 나눌 수 있다2). 부신 피질 기능 저하 증세만을 보이는 Addison's disease only ALD의 경우 주로 2세에서 7.5세에 발생하며, 증세는 구토, 위약, 혼수, ACTH 분비 증가에 따른 색소 과다 침착(hyperpigmentation)으로 나타나고 발생 당시에는 신경학적 증세가 동반되지 않는다. 저자들은 구역, 구토, 탈수, 저혈당 및 저혈압 등의 증상 없이 색소 과다 침착이 부신 피질 기능 저하의 유일한 증세였던 환아를 혈장 VLCFA 검사를 통해 X-ALD로 진단하였고, ABCD1 유전자 분석 검사에서 c.1992-2A>G 변이를 확인하였다. 국내에서 색소 과다 침착만을 보이는 환아가 X-ALD로 진단받은 보고는 찾을 수 없었으며, 국내에서 보고되지 않은 돌연변이로 이를 보고하는 바이다. X-ALD 환아의 장기적인 예후 예측과 자세한 상담을 위해서 유전자형과 표현형의 상관관계에 대한 더 많은 연구가 필요하며, 이를 위해 유전자형에 따른 증상과 예후에 대한 자료가 공유되어야 할 것이다.

• 생명과학회지
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• 제31권5호
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• pp.464-474
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• 2021

대사성질환, 암, 손상, 및 패혈증 등에 의해 유도되는 염증은 산화스트레스를 통해 세포의 미토콘드리아의 기능을 감퇴시켜 신경증과 근육위축증 등을 야기한다. 본 연구에서는 lipopolysaccharide (LPS)에 의해 유도된 미토콘 드리아의 기능감퇴와 근육위측증에 대한 butyrate의 억제효과를 확인하고자 하였다. LPS의 처리는 C2C12세포에서 MAPK의 활성을 통해 미토콘드리아 분열을 촉진하는 DRP1 (Ser616) 인산화와 Atrogin-1의 발현을 증가시켰다. 그러나 butyrate를 처리한 C2C12세포에서는 LPS 처리에 의한 염증 효과가 유의적으로 감소하며, 미토콘드리아 분열을 억제하는 DRP1 (Ser637)의 인산화와 mitofugin2 (Mfn2)의 발현을 증가를 유도하는 것을 확인하였다. 또한 butyrate를 처리한 세포에서 대사성질환을 유발하는 pyruvate dehydrogenase kinase 4 (PDK4)의 발현을 억제함이 관찰되었다. 이는 butyrate가 포도당 대사에서 염증에 의해 유도되는 Warburg 효과를 억제하여 산화스트레스를 개선함으로써, JNK의 활성을 억제하는 것으로 확인되었다. 이러한 결과들은 butyrate가 항산화효과를 통해 패혈증과 대사성질환과 같은 염증에 의해 유도되는 미토콘드리아의 기능 감퇴와 이에 따른 근육위축증을 개선할 수 있는 후보물질로 활용될 가능성이 있을 것으로 기대된다.

• BMB Reports
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• 제54권5호
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• pp.266-271
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• 2021

Estrogen-related receptor γ (ERRγ), a member of the orphan nuclear receptor family, is a key mediator in cellular metabolic processes and energy homeostasis. Therefore, ERRγ has become an attractive target for treating diverse metabolic disorders. We recently reported that ERRγ acts as a negative regulator of osteoclastogenesis induced by receptor activator of nuclear factor-κB ligand (RANKL). In the present study, we explored the effects of an ERRγ-specific modulator, GSK5182, on ERRγ-regulated osteoclast differentiation and survival. Interestingly, GSK5182 increased ERRγ protein levels much as does GSK4716, which is an ERRγ agonist. GSK5182 inhibited osteoclast generation from bone-marrow-derived macrophages without affecting cytotoxicity. GSK5182 also attenuated RANKL-mediated expression of cFos and nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), pivotal transcription factors for osteoclastogenesis. Arrested osteoclast differentiation was associated with reduced RANK expression, but not with the M-CSF receptor, c-Fms. GSK5182 strongly blocked the phosphorylation of IκBα, c-Jun N-terminal kinase, and extracellular signal-regulated kinase in response to RANKL. GSK5182 also suppressed NF-κB promoter activity in a dose-dependent manner. In addition to osteoclastogenesis, GSK5182 accelerated osteoclast apoptosis by caspase-3 activation. Together, these results suggest that GSK5182, a synthetic ERRγ modulator, may have potential in treating disorders related to bone resorption.

• Nutrition Research and Practice
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• 제17권4호
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• pp.616-630
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• 2023

BACKGROUND/OBJECTIVES: Indole-3-propionic acid (IPA) is a tryptophan-derived microbial metabolite that has been associated with protective effects against inflammatory and metabolic diseases. However, there is a lack of knowledge regarding the effects of IPA under physiological conditions and at the intestinal level. MATERIALS/METHODS: Human intestinal epithelial Caco-2 cells were treated for 2, 24, and/or 72 h with IPA or its precursors - indole, tryptophan, and propionate - at 1, 10, 100, 250, or 500 μM to assess cell viability, integrity, differentiation, and proliferation. RESULTS: IPA induced cell proliferation and this effect was associated with a higher expression of extracellular signal-regulated kinase 2 (ERK2) and a lower expression of c-Jun. Although indole and propionate also induced cell proliferation, this involved ERK2 and c-Jun independent mechanisms. On the other hand, both tryptophan and propionate increased cell integrity and reduced the expression of claudin-1, whereas propionate decreased cell differentiation. CONCLUSIONS: In conclusion, these findings suggested that IPA and its precursors distinctly contribute to the proliferation, differentiation, and barrier function properties of human intestinal epithelial cells. Moreover, the pro-proliferative effect of IPA in intestinal epithelial cells was not explained by its precursors and is rather related to its whole chemical structure. Maintaining IPA at physiological levels, e.g., through IPA-producing commensal bacteria, may be important to preserve the integrity of the intestinal barrier and play an integral role in maintaining metabolic homeostasis.

• Preventive Nutrition and Food Science
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• 제7권3호
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• pp.332-345
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• 2002

It is a recent observation that about 80 per cent of the body's immune system is localized in the gastrointestinal tract. This explains to a large extent why eating right is important for the modulation the immune response and prevention of disease. In addition it is increasingly recognized that the body has an important digestive system also in the lower gastrointestinal tract where numerous important substances are released by microbial enzymes and absorbed. Among these substances are short chain fatty acids, amino acids, various carbohydrates, poly-amines, growth factors, coagulation factors, and many thousands of antioxidants, not only traditional vitamins but numerous flavonoids, carotenoids and similar plant- and vegetable produced antioxidants. Also consumption of health-promoting bacteria (probiotics) and vegetable fibres (prebiotics) from numerous sources are known to have strong health-promoting influence. It has been calculated that the intestine harbours about 300,000 genes, which is much more than the calculated about 60,000 for the rest of the human body, indicating a till today totally unexpected metabolic activity in this part of the GI tract. There are seemingly several times more active enzymes in the intestine than in the rest of the body, ready to release hundred thousand or more of substances important for our health and well-being. In addition do the microbial cells produce signal molecules similar to cytokines but called bacteriokines and nitric oxide, with provide modulatory effects both on the mucosal cells, the mucosa- associated lymphoid system (MALT) and the rest of the immune system. Identification of various fermentation products, and often referred to as synbiotics, studies of their role in maintaining health and well-being should be a priority issue during the years to come.

• BMB Reports
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• 제38권6호
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• pp.650-660
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• 2005

Proteins accumulated in dry, stratified Arabidopsis seeds or young seedlings, totaled 1100 to 1300 depending on the time of sampling, were analyzed by using immobilized pH gradient 2-DE gel electrophoresis. The molecular identities of 437 polypeptides, encoded by 355 independent genes, were determined by MALDI-TOF or TOF-TOF mass spectrometry. In the sum, 293 were present at all stages and 95 were accumulated during the time of radicle protrusion while another 18 appeared in later stages. Further analysis showed that 226 of the identified polypeptides could be located in different metabolic pathways. Proteins involved in carbohydrate, energy and amino acid metabolism constituted to about 1/4, and those involved in metabolism of vitamins and cofactors constituted for about 3% of the total signal intensity in gels prepared from 72 h seedlings. Enzymes related to genetic information processing increased very quickly during early imbibition and reached highest level around 30 h of germination.

• BMB Reports
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• 제39권4호
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• pp.400-405
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• 2006

A 16-month old boy was referred to our hospital for evaluation of recurrent generalized tonic clonic seizures. Metabolic evaluation revealed significant hyperammonemia ($1,112\;{\mu}g/dl$). Amino acid/acylcarnitine screening using tandem mass spectrometry showed markedly increased plasma levels of citrulline ($1,350\;{\mu}M/l$) with undetectable levels of arginine and arginosuccinic acid. Urinary excretion of citrulline was markedly increased ($38,617\;{\mu}M/g$ creatinine). Brain MRI findings showed diffuse high-signal intensity lesions, that involved gray and white matter in both frontal lobes and insula with edematous changes; these findings were consistent with the acute stage of citrullinemia (CTLN). Mutation analysis of the argininosuccinate synthetase (ASS) gene, in this patient, showed a Gly324Ser mutation in exon 13, and a 67-bp duplication mutation in exon 15 (c.1128-6_1188dup67). The patient was confirmed as having late-onset CTLN1 and treated with anticonvulsants, lactulose enema, protein restricted diet and arginine. Here we describe a case of late-onset CTLN1 in a patient by biochemical analyses and ASS gene mutation confirmation. This is the first report of a Korean patient with late-onset CTLN1 confirmed by ASS gene mutation identification.