• Journal of Ginseng Research
• /
• 제46권6호
• /
• pp.750-758
• /
• 2022

Background: Mild cognitive impairment (MCI) is a transitional condition between normality and dementia. Ginseng is known to have effects on attenuating cognitive deficits in neurogenerative diseases. Ginsenosides are the main bioactive component of ginseng, and their protein targets have not been fully understood. Furthermore, no thorough analysis is reported in ginsenoside-related protein targets in MCI. Methods: The candidate protein targets of ginsenosides in brain tissues were identified by drug affinity responsive target stability (DARTS) coupled with label-free liquid chromatography-mass spectrometry (LC-MS) analysis. Network pharmacology approach was used to collect the therapeutic targets for MCI. Based on the above-mentioned overlapping targets, we built up a proteineprotein interaction (PPI) network in STRING database and conducted gene ontology (GO) enrichment analysis. Finally, we assessed the effects of ginseng total saponins (GTS) and different ginsenosides on mitochondrial function by measuring the activity of the mitochondrial respiratory chain complex and performing molecular docking. Results: We screened 2526 MCI-related protein targets by databases and 349 ginsenoside-related protein targets by DARTS. On the basis of these 81 overlapping genes, enrichment analysis showed the mitochondria played an important role in GTS-mediated MCI pharmacological process. Mitochondrial function analysis showed GTS, protopanaxatriol (PPT), and Rd increased the activities of complex I in a dose-dependent manner. Molecular docking also predicted the docking pockets between PPT or Rd and mitochondrial respiratory chain complex I. Conclusion: This study indicated that ginsenosides might alleviate MCI by targeting respiratory chain complex I and regulating mitochondrial function, supporting ginseng's therapeutic application in cognitive deficits.

• 대한화학회지
• /
• 제67권2호
• /
• pp.99-105
• /
• 2023

Here we present how a supramolecular complex of Glycyrrhizic acid (GA) with Menthol (Mt) affects the blood glucose levels and glycogen synthesis in the liver of rats in in-vivo experiments with diabetes caused by alloxan. We have shown that Menthol, Glycyrrhizic acid and GA:Mt supramolecular complexes can restore functional dysfunction of the liver mitochondria in alloxan diabetes, i.e., inhibit lipid peroxidation. The hypoglycemic activity and mitochondrial membrane stabilizing properties of the supramolecular complex GA:Mt (4:1) in alloxan diabetes were more pronounced than those of menthol, GA and its GA:Mt (2:1) and GA: Mt (9:1) supramolecular complexes.

• Genes and Genomics
• /
• 제40권11호
• /
• pp.1169-1180
• /
• 2018

Cave shrimps from the genera Typhlatya, Stygiocaris and Typhlopatsa (TST complex) comprises twenty cave-adapted taxa, which mainly occur in the anchialine environment. Anchialine habitats may undergo drastic environmental fluctuations, including spatial and temporal changes in salinity, temperature, and dissolved oxygen content. Previous studies of crustaceans from anchialine caves suggest that they have possessed morphological, behavioral, and physiological adaptations to cope with the extreme conditions, similar to other cave-dwelling crustaceans. However, the genetic basis has not been thoroughly explored in crustaceans from anchialine habitats, which can experience hypoxic regimes. To test whether the TST shrimp-complex hypoxia adaptations matched adaptive evolution of mitochondrial OXPHOS genes. The 13 OXPHOS genes from mitochondrial genomes of 98 shrimps and 1 outgroup were examined. For each of these genes was investigated and compared to orthologous sequences using both gene (i.e. branch-site and Datamonkey) and protein (i.e. TreeSAAP) level approaches. Positive selection was detected in 11 of the 13 candidate genes, and the radical amino acid changes sites scattered throughout the entire TST complex phylogeny. Additionally, a series of parallel/convergent amino acid substitutions were identified in mitochondrial OXPHOS genes of TST complex shrimps, which reflect functional convergence or similar genetic mechanisms of cave adaptation. The extensive occurrence of positive selection is suggestive of their essential role in adaptation to hypoxic anchialine environment, and further implying that TST complex shrimps might have acquired a finely capacity for energy metabolism. These results provided some new insights into the genetic basis of anchialine hypoxia adaptation.

• 한국동물학회지
• /
• 제31권1호
• /
• pp.62-70
• /
• 1988

미토콘드리아가 포함하고있는 결정한유물의 미새구조와 면역황금표식법에 의한 분석을 위하여 우심근 세포의 미토콘드리아에서 전자전달체에 관여하는 효소를 분리하였다. 우심근 미토콘드리아에서 분리된 효소는 실험토끼에 주사하여 (복합체I,NADH-conezyme Q reductase; 복합체 III,Ubiquinol-cytochrome-c-oxldoreductase; 복합체 IV, Cytochrome-c-oxidase)들에 대한 면역항체를 얻었다. 이들 면역항체들은 우심근과 정상인의 골격근 미토콘드리아와 미토콘드리아에 결정함유물을 포함하는 mitochondrical myopathy환자의 골격근 미토콘드리아에 반응시켜 황금입자를 표식하고 전자현미경을 이용하여 이들 면역항체반응을 관찰하였다. 미토콘드리아가 포함하는 결정함유물의 미세구조에는 paracrystalline inclusions body와 multilamellar strudure inclusion body그리고 구형결정함유물(globular crystalline inclusions body) 및 윤형구조 (whirl shaped structure)의 크리스테 중심에 있는 구형결정함유물 등의 4종류로관찰되었다. 복합체 I,복합체 Iv의 효소에 대한 항체를 우심근과 정상인 골격근 그리고 mitochondrical myopathy환자의 골격근에 동일한 면역반응을 시켰을때 미토콘드리아 크리스테에 부착하는 황금입자의 표식 정도는 각각의 근조직에서 유사한 반응이 관찰되었다. 복합체 III의 효소에 대한 항체는 우심근과 정상인의 골격근에서는 유사한 반응이 나타났으나 mitochondrical myopathy환자의 골격근에서는 극히 소수의 황금입자가 관찰되었다. 구형결정함유물은 복합체 I,III,IV의 3종류의 효소에 대한 면역반응 결과 황금입자표식은 관찰되지 않았다. 따라서 mitochondrical myopathy환자의 미토콘드리아에는 복합에 III의 효소가 결핍되었으며 구형결정함유물은 전자전달체 효소들인 복합체 I,III,Iv 효소단백질과는 상관없는 물질로 생각된다.

• Asian-Australasian Journal of Animal Sciences
• /
• 제24권6호
• /
• pp.857-866
• /
• 2011

This study examined the metabolism of free radicals in hepatic mitochondria of goats induced by lipopolysaccharide (LPS), and investigated the effects of melatonin (MT). Forty-eight healthy goats ($10{\pm}1.2\;kg$) were randomly selected and divided into four groups: saline control, LPS, MT+LPS and MT. The goats within each group were3 sacrificed either 3 or 6 h after treatment and the livers removed to isolate mitochondria. The respiration control ratio (RCR), the ADP:O ratio, the oxidative phosphorylation ratio (OPR), the concentration of $H_2O_2$ and the activities of Complex I-IV were determined. The mitochondrial membrane potential ($\Delta\psi_m$) was analyzed by flow cytometry. The results showed that RCR, O/P and OPR of the LPS group decreased (p<0.05), as well as activities of respiratory complexes, whereas the generation of $H_2O_2$ in Complex III increased (p<0.05) after 3 h, while Complex II and III increased after 6 h. Also, it was found that the mitochondrial membrane potential of the LPS group declined (p<0.05). However, pre-treatment with MT attenuated the injury induced by LPS, which not only presented higher (p<0.05) RCR, O/P, OPR, and respiratory complex activities, but also maintained the $\Delta\psi_m$. Interestingly, it is revealed that, in the MT+LPS group, the generation of $H_2O_2$ increased firstly in 3 h, and then significantly (p<0.05).decreased after 6 h. In the MT group, the function of mitochondria, the transmenbrane potential and the generation of $H_2O_2$ were obviously improved compared to the control group. Conclusion: melatonin prevents damage caused by LPS on hepatic mitochondria of goats.

• Animal cells and systems
• /
• 제14권2호
• /
• pp.91-98
• /
• 2010

Male rats were given a single injection of iron, and temporal changes in iron content and iron-induced effects were examined in heart cellular fractions. Over a period of 72 h, the contents of total and labile iron, reactive oxygen species, and NO in tissue homogenate, nuclear debris, and postmitochondrial fractions were mostly constant, but in mitochondria they continuously increased. An abrupt decrease in membrane potential and NAD(P)H at 12 h was also found in mitochondria. The respiratory control ratio was reduced slowly with a slight recovery at 72 h, suggesting uncoupling by iron.While the ATP content of tissue homogenate decreased steadily until 72 h, it showed a prominent increase in mitochondria at 12 h. Total iron and calcium concentration also progressively increased in mitochondria over 72 h. Enzyme activity of the oxidative phosphorylation system was significantly altered by iron injection: activities of complexes I, III, and IV were reduced considerably, but complex II activity and the ATPase activity of complex V were enhanced. A reversal of activity in complexes I and II at 12 h suggested reverse electron transfer due to iron overload. These results support the argument that mitochondrial activities including oxidative phosphorylation are modulated by excessive iron.

• The Korean Journal of Physiology and Pharmacology
• /
• 제20권2호
• /
• pp.201-211
• /
• 2016

Although the antioxidant and cardioprotective effects of NecroX-5 on various in vitro and in vivo models have been demonstrated, the action of this compound on the mitochondrial oxidative phosphorylation system remains unclear. Here we verify the role of NecroX-5 in protecting mitochondrial oxidative phosphorylation capacity during hypoxia-reoxygenation (HR). Necrox-5 treatment ($10{\mu}M$) and non-treatment were employed on isolated rat hearts during hypoxia/reoxygenation treatment using an ex vivo Langendorff system. Proteomic analysis was performed using liquid chromatography-mass spectrometry (LC-MS) and non-labeling peptide count protein quantification. Real-time PCR, western blot, citrate synthases and mitochondrial complex activity assays were then performed to assess heart function. Treatment with NecroX-5 during hypoxia significantly preserved electron transport chain proteins involved in oxidative phosphorylation and metabolic functions. NecroX-5 also improved mitochondrial complex I, II, and V function. Additionally, markedly higher peroxisome proliferator-activated receptor-gamma coactivator-$1{\alpha}$ ($PGC1{\alpha}$) expression levels were observed in NecroX-5-treated rat hearts. These novel results provide convincing evidence for the role of NecroX-5 in protecting mitochondrial oxidative phosphorylation capacity and in preserving $PGC1{\alpha}$ during cardiac HR injuries.

• 대한유전성대사질환학회지
• /
• 제18권3호
• /
• pp.95-98
• /
• 2018

미토콘드리아 질환은 단일 장기에서부터 여러 장기에 걸쳐 침범할 수 있다는 임상 증상의 광범위한 이질성이 특징이다. 안검하수, 색소 망막 퇴화, 외안근 마미, 시신경 위축 등과 같은 다양한 안구 증상이 미토콘드리아 질환에서 함께 나타날 수 있지만, 진행성 양안 백내장은 미토콘드리아 질환의 안과적 증상에서 매우 드물다. 저자들은 미토콘드리아 호흡 연쇄 복합체 결핍 환자에서 흔치 않은 안구 발현 현상인 진행성 양안 백내장 침범 사례를 경험하였기에 보고하는 바이다.

• Molecules and Cells
• /
• 제42권4호
• /
• pp.292-300
• /
• 2019

Immunometabolism, defined as the interaction of metabolic pathways with the immune system, influences the pathogenesis of metabolic diseases. Metformin and carbon monoxide (CO) are two pharmacological agents known to ameliorate metabolic disorders. There are notable similarities and differences in the reported effects of metformin and CO on immunometabolism. Metformin, an anti-diabetes drug, has positive effects on metabolism and can exert anti-inflammatory and anti-cancer effects via adenosine monophosphate-activated protein kinase (AMPK)-dependent and AMPK-independent mechanisms. CO, an endogenous product of heme oxygenase-1 (HO-1), can exert anti-inflammatory and antioxidant effects at low concentration. CO can confer cytoprotection in metabolic disorders and cancer via selective activation of the protein kinase R-like endoplasmic reticulum (ER) kinase (PERK) pathway. Both metformin and CO can induce mitochondrial stress to produce a mild elevation of mitochondrial ROS (mtROS) by distinct mechanisms. Metformin inhibits complex I of the mitochondrial electron transport chain (ETC), while CO inhibits ETC complex IV. Both metformin and CO can differentially induce several protein factors, including fibroblast growth factor 21 (FGF21) and sestrin2 (SESN2), which maintain metabolic homeostasis; nuclear factor erythroid 2-related factor 2 (Nrf2), a master regulator of the antioxidant response; and REDD1, which exhibits an anticancer effect. However, metformin and CO regulate these effects via different pathways. Metformin stimulates p53- and AMPK-dependent pathways whereas CO can selectively trigger the PERK-dependent signaling pathway. Although further studies are needed to identify the mechanistic differences between metformin and CO, pharmacological application of these agents may represent useful strategies to ameliorate metabolic diseases associated with altered immunometabolism.

• 한국수정란이식학회지
• /
• 제18권3호
• /
• pp.227-235
• /
• 2003

한우의 mt DNA cytochrome oxidase subunit I, II, 및 III complex지역의 유전적 다형현상을 제한효소를 이용하여 검출하였다. PCR primer 6종에 대하여 20가지 제한효소를 처리하였으며, Pst I, Pvu II, Rsa I, Eco RI, Bgl II, and Msp I 제한효소를 사용하여 유전적 변이를 검출하였다. 검출된 변이체와 한우의 성장과의 관련성을 조사한 결과 cytochrome oxidase subunit III complex 지역의 유전염기서열을 근거로 제작한 primer Mt9 좌위에서 제한효소 PvuII를 이용한 절단형과 체중형질 인 WT15(P<0.05) 및 WT18(P<0.01)에서 고도의 유의성이 관찰되었다. 아울러 , Mt9-Pvu II(P=0.07), Mt6-Bgl II(P=0.05), and Mt8-Rsa I(P=0.05) 좌위 또한 WT9, WTl5, and WT15에서 각각 통계적 유의성이 관찰되었다. 따라서 본 결과는 cytochrome oxidase subunit III complex segments가 candidate gene으로서 기초적 유전정 보 제공은 물론 유전적 개량을 위해 사용될 수 있을 것으로 사료된다.