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Therapeutic effects of exogenous glucosamine
Inn-Oc Han 한국당과학회 2022 한국당과학회 학술대회 Vol.2022 No.07
The hexosamine biosynthesis pathway (HBP) is an important branch of glycolysis to induced protein O-GlcNAcylation and acts as a glucose sensing in many types of cells. Glucosamine (alternatively named 2-amino-2-deoxy-d-glucose), an intermediate metabolite of the HBP, bypasses glycolysis for directly entering HBP. Since glucosamine stimulates glycosaminoglycan production, it has been extensively studied in the context of osteoarthritis and joint pain. Although several clinical studies conducted on oral supplementation of glucosamine demonstrate its beneficial effects in the progression of osteoarthritis and cartilage renewal, the efficacy of glucosamine for osteoarthritis remains controversial. Furthermore, exogenous glucosamine application exhibits therapeutic effects by increasing protein O-GlcNAcylation. Glucosamine regulates glucose metabolism, insulin resistance, diabetic complications and lipid metabolism. Additionally, glucosamine exerts several beneficial effects on oxidative stress, inflammation, cell proliferation, apoptosis, and growth factor signaling. More recent studies demonstrate that exogenous glucosamine can improve the neurodegeneration and cognitive function induced by sleep deprivation, circadian cycle disruption and hypoxia, emerging glucosamine as a therapeutic benefit for neuronal dysfunction. However, whether increased O-GlcNAcylation by exogenous glucosamine is protective to disease or promotes progression of the disease or is still a matter of debate. Due to the abundance and ubiquitous nature of the HBP and protein O-GlcNAcylation in mammalian cells and potential effects to other signaling pathways, exogenous glucosamine may induce various effects depends on doses, metabolic status, cell and tissue types and species.
쥐의 간 미토콘드라아의 Aldehyde Dehydrogenase 의 정제 및 특성에 관한 연구
한인옥,주충노 ( Inn Oc Han,Chung No Joo ) 생화학분자생물학회 1991 BMB Reports Vol.24 No.4
Rat liver mitochondrial aldehyde dehydrogenase isozymes were purified and characterized. Purification of rat liver mitochondrial aldehyde dehydrogenase (ALDH) isozymes were carried out by Sephadex G-150, DEAE-Sephael and 5`-AMP Sepharose 4B chromatography. Three isozymes, membrane bound ALDH and soluble high K_m ALDH (ALDH-I) and low K_m ALDH (ALDH-II) were obtained. Molecular weights of native membrane bound ALDH, ALDH-I and matrix ALDH-II were identified to be 237 kilodaton (kD), 234 kD and 204 kD by Sephacryl S-300 column chromatography. K_m of the mitochondrial membrane for short chain aliphatic aldehydes bound ALDH was higher (10^(-2)∼10^(-3) M level) than those for aromatic aldehydes including biogenic aldehydes (10^(-5)M level) suggesting that the membrane ALDH might act as barrier against aromatic aldehydes. On the hand, the K_m of the mitochondrial low K_m ALDH (matrix ALDH-II) for short chain aliphatic aldehydes were extremely low (10^(-6)M), however, both ALDH-I and ALDH-II did not work on biogenic aldehydes. K_ms of cytosolic ALDH for both aliphatic and aromatic aldehydes were all 10^(-4) M level. It is concluded that aldehydes formed in cytosol might be metabolized down to 10^(-5)M level and the short chain aliphatic aldehydes enter into mitochondrial matrix where they might be oxidized while aromatic aldehydes including biogenic aldehydes would be oxidized by the mitochondrial membrane bound ALDH.
Purification and Characterization of the Rat Liver Mitochondrial Aldehyde Dehydrogenases
한인옥,주충노,Han, Inn-Oc,Joo, Chung-No Korean Society for Biochemistry and Molecular Biol 1991 한국생화학회지 Vol.24 No.4
쥐의 간 미토콘드리아의 세 가지 aldehyde dehydrogenase (ALDH) isozyme을 Sephadex G-150, DEAE-Sephacel, 5'-AMP Sepharose 4B chromatography법을 이용하여 정제하고 특성을 조사하였다. 미토콘드리아의 막결합 ALDH, 가용성 ALDH-I과 ALDH-II의 분자량을 Sephacryl S-300 column ascending chromatography로 측정한 결과 각각 237 kD, 224 kD, 204 kD였다. 미토콘드리아의 막결합 ALDH의 저급 지방족 aldehyde에 대한 $K_m$은 $10^{-2}{\sim}10^{-3}M$ 수준으로 비교적 높으나 생체 생성 aldehyde같은 방향족 aldehyde에 대한 $K_m$은 아주 낮은 ($10^{-5}M$ 수준) 것으로 보아 막결합 ALDH는 방향족 aldehyde에 대한 barrier의 구실을 하는 것으로 예상된다. 한편 탄소수가 적은 지방족 aldehyde에 대한 유리형의 ALDH II의 $K_m$값은 이주 낮다($10^{-6}M$ 수준). 그러나 가용성 ALDH I과 ALDH II는 모두 biogenic aldehyde와는 작용하지 않는다. 지방족이나 방향족 aldehyde에 대한 시토솔 ALDH의 $K_m$은 모두 $10^{-4}M$ 수준이다. 이상과 같은 실험 결과로 보아 aldehyde들은 시토솔에서 $10^{-5}M$ 수준까지 대사된 후 짧은 지방족 aldehyde는 미토콘드리아 내부로 침투되어 산화되지만 biogenic aldehyde와 같은 방향족 aldehyde는 미토콘드리아의 막결합 ALDH에 의해 산화되는 것으로 생각된다. Rat liver mitochondrial aldehyde dehydrogenase isozymes were purified and characterized. Purification of rat liver mitochondrial aldehyde dehydrogenase (ALDH) isozymes were carried out by Sephadex G-150, DEAE-Sephael and 5'-AMP Sepharose 4B chromatography. Three isozymes, membrane bound ALDH and soluble high $K_m$ ALDH (ALDH-I) and low $K_m$ ALDH (ALDH-II) were obtained. Molecular weights of native membrane bound ALDH, ALDH-I and matrix ALDH-II were identified to be 237 kilodaton (kD), 234 kD and 204 kD by Sephacryl S-300 column chromatography. $K_m$ of the mitochondrial membrane for short chain aliphatic aldehydes bound ALDH was higher ($10^{-2}{\sim}10^{-3}M$ level) than those for aromatic aldehydes including biogenic aldehydes ($10^{-5}M$ level) suggesting that the membrane ALDH might act as barrier against aromatic aldehydes. On the hand, the $K_m$ of the mitochondrial low $K_m$ ALDH (matrix ALDH-II) for short chain aliphatic aldehydes were extremely low ($10^{-6}M$), however, both ALDH-I and ALDH-II did not work on biogenic aldehydes. $K_ms$ of cytosolic ALDH for both aliphatic and aromatic aldehydes were all $10^{-4}M$ level. It is concluded that aldehydes formed in cytosol might be metabolized down to $10^{-5}M$ level and the short chain aliphatic aldehydes enter into mitochondrial matrix where they might be oxidized while aromatic aldehydes including biogenic aldehydes would be oxidized by the mitochondrial membrane bound ALDH.
Synthesis and Evaluation of Biological Properties of Benzylideneacetophenone Derivatives
오세관,Soyong Jang,Donghyun Kim,Inn-Oc Han,Jae-Chul Jung 대한약학회 2006 Archives of Pharmacal Research Vol.29 No.6
A series of yakuchinone B 1f and its analogs 1a-e was synthesized and evaluated for free radical scavenging, suppression of LPS-induced NO generation, cytotoxicity and anti-excitotoxicity in vitro. Compound 1c exhibited potent anti-excitotoxicity, while all compounds 1a-f showed considerable effects of free radical scavenging, suppression of LPS–induced NO generation, and cytotoxicity in microglia.