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KCa 3.1 upregulation preserves endothelium-dependent vasorelaxation during aging and oxidative stress


, : KCa 3.1 upregulation preserves endothelium-dependent vasorelaxation during aging and oxidative stress. Aging Cell 15(5): 801-810

Endothelial oxidative stress develops with aging and reactive oxygen species impair endothelium-dependent relaxation (EDR) by decreasing nitric oxide (NO) availability. Endothelial KCa 3.1, which contributes to EDR, is upregulated by H2 O2 . We investigated whether KCa 3.1 upregulation compensates for diminished EDR to NO during aging-related oxidative stress. Previous studies identified that the levels of ceramide synthase 5 (CerS5), sphingosine, and sphingosine 1-phosphate were increased in aged wild-type and CerS2 mice. In primary mouse aortic endothelial cells (MAECs) from aged wild-type and CerS2 null mice, superoxide dismutase (SOD) was upregulated, and catalase and glutathione peroxidase 1 (GPX1) were downregulated, when compared to MAECs from young and age-matched wild-type mice. Increased H2 O2 levels induced Fyn and extracellular signal-regulated kinases (ERKs) phosphorylation and KCa 3.1 upregulation. Catalase/GPX1 double knockout (catalase(-/-) /GPX1(-/-) ) upregulated KCa 3.1 in MAECs. NO production was decreased in aged wild-type, CerS2 null, and catalase(-/-) /GPX1(-/-) MAECs. However, KCa 3.1 activation-induced, N(G) -nitro-l-arginine-, and indomethacin-resistant EDR was increased without a change in acetylcholine-induced EDR in aortic rings from aged wild-type, CerS2 null, and catalase(-/-) /GPX1(-/-) mice. CerS5 transfection or exogenous application of sphingosine or sphingosine 1-phosphate induced similar changes in levels of the antioxidant enzymes and upregulated KCa 3.1. Our findings suggest that, during aging-related oxidative stress, SOD upregulation and downregulation of catalase and GPX1, which occur upon altering the sphingolipid composition or acyl chain length, generate H2 O2 and thereby upregulate KCa 3.1 expression and function via a H2 O2 /Fyn-mediated pathway. Altogether, enhanced KCa 3.1 activity may compensate for decreased NO signaling during vascular aging.

US$19.90

PMID: 27363720

DOI: 10.1111/acel.12502


Other references

Kirchner, Hch, 1927: Footprints in sandstone in Franconia, Germany. These footprints differ from Chirotherium barthi of Thuringia and are described as C. vorbachi* (p. 117) and Saurich-nites auraensis* (p. 119). Types in Deutsch. Geol. Gesell., Stuttgart.

Cortelyou, R.G. ., 1985: 1985 Sixtieth spring occurrence report. Nebraska Bird Review, 533: 50-66

Knaus, E.; Höchtl, G., 1970: Artificial insemination of the pig. Wiener Tierarztliche Monatsschrift 57(12): 420-422

Crantz, F.R.; Swartz, S.L.; Hollenberg, N.K.; Moore, T.J.; Dluhy, R.G.; Williams, G.H., 1980: Differences in response to the peptidyldipeptide hydrolase inhibitors SQ 20,881 and SQ 14,225 in normal-renin essential hypertension. We compared vascular and hormonal responses to teprotide (SQ 20,881) and captopril (SQ 14,225) in patients with normal renin essential hypertension given a 10 mEq sodium diet. In 10 patients receiving SQ 20,881, significant changes occurred in dia...

Cubillos, A.; Fuschlocher, R., 1981: Combination of rapeseed (Brassica napus) and barley in the feeding of broilers. I. Nutritional aspects. A total of 160 chicks were distributed into three experimental and control groups. Each group had two blocks, males and females, and during their two growing periods of 0-40 and 41-70 days, the four groups received isocaloric and isoproteic diets....

Mclaughlin, J.; Sinclair, N.; Colucci, R.; Raychowdery, R.; Wang, T.; Koh, T., 2002: Pituitary adenylate cyclase-activating polypeptide and gastrin regulate the histidine decarboxylase promoter via distinct mechanisms. Regulatory Peptides 108(1): 19-20, 15 August

Einszporn Orecka T., 1970: Quantitative changes in the circulating blood of tench tinca tinca in the annual cycle. Polskie Archiwum Hydrobiologii 17(4): 435-444

Amine, E.K.; al-Awadi, F., 1991: Factors affecting birth weight in Kuwait. Part I, Maternal, dietary and socioeconomic factors. The aim of this study was to determine the effect of maternal nutrition, vitamin supplementation and socioeconomic status on infants birth weight in Kuwait. The weight of 1995 newborn Kuwaiti infants was recorded shortly after delivery. Data on mo...

Luttrell B.; Waters S., 1991: Computerized method for validating laboratory reference ranges for triiodothyronine and thyroxine immunoassays. We used a computer-based method to help validate the reference ranges of assays for triiodothyronine (T3) and thyroxin (T4). A retrospective search of a data base of laboratory results for the previous six months identified all patients with appar...

Muthukumaraswamy, S.D.; Singh, K.D., 2008: Modulation of the human mirror neuron system during cognitive activity. In this experiment we examined the relationship between the mirror neuron system and increased attention caused by task demands. Whole head MEG recordings were made from 13 participants who were asked to passively observe finger movement sequences...