title: Vitamin C attenuates hypochlorite-mediated loss of paraoxonase-1 activity from human plasma.
abstract: Paraoxonase 1 (PON1) is a cardioprotective enzyme associated with high-density lipoprotein (HDL). We tested the hypothesis that vitamin C protects HDL and PON1 from deleterious effects of hypochlorous acid, a proinflammatory oxidant. In our experiments, HDL (from human plasma) or diluted human plasma was incubated with hypochlorite in either the absence (control) or presence of vitamin C before measuring chemical modification and PON1 activities. Vitamin C minimized chemical modification of HDL, as assessed by lysine modification and accumulation of chloramines. In the absence of vitamin C, chloramines accumulated to 114 +/- 4 micromol/L in HDL incubated with a 200-fold molar excess of hypochlorite; but addition of vitamin C (200 micromol/L) limited formation to 36 +/- 6 micromol/L (P < .001). In plasma exposed to hypochlorite, IC(50) values of 1.2 +/- 0.1, 9.5 +/- 1.0, and 5.0 +/- 0.6 mmol/L were determined for PON1's phosphotriesterase, arylesterase, and (physiologic) lactonase activities, respectively. Vitamin C lessened this inhibitory effect of hypochlorite on PON1 activities. In plasma supplemented with vitamin C (400 micromol/L), PON1 phosphotriesterase activity was 72% +/- 17% of normal after incubation with hypochlorite (2 mmol/L), compared with 42% +/- 6% for unsupplemented plasma (P < .05). Similar effects were seen for other PON1 activities. In some experiments, vitamin C also appeared to reverse hypochlorite-mediated loss of PON1 phosphotriesterase activity; but this effect was not observed for the other PON1 activities. In conclusion, vitamin C attenuated hypochlorite-mediated loss of PON1 activity in vitro and may, therefore, preserve cardioprotective properties of HDL during inflammation.
authors.affiliation: College of Health Sciences, Midwestern University, Downers Grove, IL 60515, USA.
authors.forename: Jacob P
authors.initials: JP
authors.lastname: Kunes
authors.forename: Katie S
authors.initials: KS
authors.lastname: Cordero-Koning
authors.forename: Lionel H
authors.initials: LH
authors.lastname: Lee
authors.forename: Sean M
authors.initials: SM
authors.lastname: Lynch
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D043303:Aryldialkylphosphatase / Q000097:blood*; D001205:Ascorbic Acid / Q000097:blood / Q000494:pharmacology*; D002265:Carboxylic Ester Hydrolases / Q000097:blood / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000517:prevention & control; D006801:Humans; D006997:Hypochlorous Acid / Q000494:pharmacology*; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism; D044345:Phosphoric Triester Hydrolases / Q000097:blood
chemical_list: D000975:Antioxidants; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D006997:Hypochlorous Acid; D002265:Carboxylic Ester Hydrolases; C019103:delta-lactonase; C019734:arylesterase; D044345:Phosphoric Triester Hydrolases; D043303:Aryldialkylphosphatase; D001205:Ascorbic Acid