ApoA‐I mutants V156K and R173C promote anti‐inflammatory function and antioxidant activities

Cho, K H; Park, S H; Han, Jong Min; Kim, Hyoung-Chin; Choi, Yang Kyu; Choi, Inho

doi:10.1111/j.1365-2362.2006.01737.x

Cited by 37 publications

(29 citation statements)

References 30 publications

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“…Additionally, this result indicates that artificial sweetener-mediated modification is very similar to the chemical reaction of fructose. ApoA-I is well-known for its antioxidant ability in both lipid-free and lipid-bound states (Cho et al, 2006). Similarly, Liz et al (2007) reported that cleavage of apoA-I (26 kDa) by transthyretin is associated with loss of unique features of dysfunctional HDL and an increase in amyloidogenicity.…”

Section: Discussionmentioning

confidence: 99%

Modified Apolipoprotein (apo) A-I by Artificial Sweetener Causes Severe Premature Cellular Senescence and Atherosclerosis with Impairment of Functional and Structural Properties of apoA-I in Lipid-Free and Lipid-Bound State

Jang

Jeoung

Cho

2011

Molecules and Cells

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Long-term consumption of artificial sweeteners (AS) has been the recent focus of safety concerns. However, the potential risk of the AS in cardiovascular disease and lipoprotein metabolism has not been investigated sufficiently. We compared the influence of AS (aspartame, acesulfame K, and saccharin) and fructose in terms of functional and structural correlations of apolipoprotein (apo) A-I and high-density lipoproteins (HDL), which have atheroprotective effects. Long-term treatment of apoA-I with the sweetener at physiological concentration (3 mM for 168 h) resulted in loss of antioxidant and phospholipid binding activities with modification of secondary structure. The AS treated apoA-I exhibited proteolytic cleavage to produce 26 kDa-fragment. They showed pro-atherogenic properties in acetylated LDL phagocytosis of macrophages. Each sweetener alone or sweetener-treated apoA-I caused accelerated senescence in human dermal fibroblasts. These results suggest that long-term consumption of AS might accelerate atherosclerosis and senescence via impairment of function and structure of apoA-I and HDL.

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Section: Discussionmentioning

confidence: 99%

Modified Apolipoprotein (apo) A-I by Artificial Sweetener Causes Severe Premature Cellular Senescence and Atherosclerosis with Impairment of Functional and Structural Properties of apoA-I in Lipid-Free and Lipid-Bound State

Jang

Jeoung

Cho

2011

Molecules and Cells

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“…In vivo test using hypercholesterolemic mice The experimental design of the in vivo test was identical to our previous report (Cho et al, 2006). In brief, normal male C57BL/6J mice (22-24 g of body weight) were obtained at 5-weeks of age from the Jackson Laboratory (Bar Habor, ME).…”

Section: Measurement Of Cholesterol Delivery Into Hepg2 Cellsmentioning

confidence: 99%

“…§ HCHF diet containing 0.5% cholesterol/15% lard/0.1% sodium cholate. ∥ Experimental design and data were adopted from our previous report (Cho et al, 2006) Statistical analysis All data were expressed as the means ± S.D. Data was evaluated via one-way Analysis of Variance (ANOVA) using SPSS, and the differences between the means were assessed via Duncan's multiplerange test.…”

Section: Atherosclerotic Lesion Analysismentioning

confidence: 99%

“…Our study also indicated that various parameters of the two mutants were markedly different in the lipid-free and lipid-bound states, thereby suggesting that the mutants might play different physiological roles in the circulation. We then prepared four kinds of rHDL with palmitoyloleoyl phosphatidylcholine (POPC) using apoA-I and its point mutants; wildtype (WT), V156K, A158E, and R173C, and attempted to further evaluate their in vivo therapeutic potential, as recently reported (Cho et al, 2006). WT-rHDL and R173C-rHDL were used as negative and positive controls (Nissen et al, 2003), respectively, and both of these harbored an extra 6 propeptide amino acids within their N-terminal regions, as did V156K and A158E.…”

Section: Introductionmentioning

confidence: 99%

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A point mutant of apolipoprotein A-I, V156K, exhibited potent anti-oxidant and anti-atherosclerotic activity in hypercholesterolemic C57BL/6 mice

Cho

Park²,

Han³

et al. 2007

Exp Mol Med

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In our previous study, two point mutants of apolipoprotein A-I, designated V156K and A158E, revealed peculiar characteristics in their lipid-free and lipid-bound states. In order to determine the putative therapeutic potential of these mutants, several in vitro and in vivo evaluations were conducted. In the lipid-free state, V156K showed more profound antioxidant activity against LDL oxidation than did the wildtype (WT) or A158E variants in an in vitro assay. In the lipid-bound state, V156K-rHDL showed an enhanced cholesterol delivery activity to HepG2 cells in a time-dependent manner, as compared to WT-rHDL, A158E-rHDL, and R173C-rHDL. We assessed the physiological activities of the mutants in circulation, using hypercholesterolemic mice (C57BL6/J). Palmitoyloleoyl phosphatidylcholine (POPC)-rHDL preparations containing each of the apoA-I variants were injected into the mice at a dosage of 30 mg of apoA-I/kg of body weight. Forty eight hours after injection, the sera of the V156K-rHDL injected group showed the most potent antioxidant abilities in the ferric acid removal assay. The V156K-rHDL-or R173C-rHDL-injected mice showed no atherosclerotic lesions and manifested striking increases in their serum apo-E levels, as compared to the mice injected with WT-rHDL or A158E-rHDL. In conclusion, V156K-rHDL exhibited the most pronounced antioxidant activity and anti-atherosclerotic activity, both in vitro and in vivo. These results support the notion that HDL-therapy may prove beneficial due to its capacity to induce accelerated cholesterol excretion, as well as its enhanced antioxidant and anti-inflammatory effects and lesion regression effect.

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“…Purification of WT and V156K apoA-I WT and V156K apoA-I were expressed in an E. coli expression system and then purified using Ni 2+ -column chromatography as described previously (Cho et al, 2006;Han et al, 2005). Protein purity was assessed by 20% sodium dodecyl sulfate-poly acrylamide gel electrophoresis using a Pharmacia Phast System (Uppsala, Sweden).…”

Section: Methodsmentioning

confidence: 99%

A Proteoliposome Containing Apolipoprotein A-I Mutant (V156K) Enhances Rapid Tumor Regression Activity of Human Origin Oncolytic Adenovirus in Tumor-Bearing Zebrafish and Mice

Seo

Yun

Kwon

et al. 2012

Molecules and Cells

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ApoA‐I mutants V156K and R173C promote anti‐inflammatory function and antioxidant activities

Abstract: The V156K-rHDL and R173C-rHDL displayed potent beneficial effects, including anti-oxidant and anti-inflammatory activity from both in vitro and in vivo evaluations, whereas the WT-rHDL and A158E-rHDL did not.

Cited by 37 publications

References 30 publications

Modified Apolipoprotein (apo) A-I by Artificial Sweetener Causes Severe Premature Cellular Senescence and Atherosclerosis with Impairment of Functional and Structural Properties of apoA-I in Lipid-Free and Lipid-Bound State

Modified Apolipoprotein (apo) A-I by Artificial Sweetener Causes Severe Premature Cellular Senescence and Atherosclerosis with Impairment of Functional and Structural Properties of apoA-I in Lipid-Free and Lipid-Bound State

A point mutant of apolipoprotein A-I, V156K, exhibited potent anti-oxidant and anti-atherosclerotic activity in hypercholesterolemic C57BL/6 mice

A Proteoliposome Containing Apolipoprotein A-I Mutant (V156K) Enhances Rapid Tumor Regression Activity of Human Origin Oncolytic Adenovirus in Tumor-Bearing Zebrafish and Mice

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