PKC-δ isozyme gene silencing restores vascular function in diabetic rats
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Kateryna Klymenko
Abstract
Background: Endothelium and K+ channel functionality in smooth muscle cells (SMCs) regulates vascular function and is exposed to damage in diabetes. The regulatory enzyme protein kinase C (PKC) is known to play a key role in vascular tone regulation in health and disease. In this study, we evaluated the effect of PKC-δ gene silencing using small interfering RNAs (siRNAs) on endothelial dysfunction and acquired potassium channelopathy in vascular SMCs in diabetes.
Methods: The experimental design comprised diabetes induction by streptozotocin (65 mg/kg) in rats, RNA interference, isolated aortic ring contractile recordings, whole-cell patch-clamp technique, measurements of reactive oxygen species (ROS), and real-time polymerase chain reaction technique. Animals were killed by cervical dislocation following ketamine (45 mg/kg, i.p.) and xylazine (10 mg/kg, i.p.) anesthesia administration on the third month of diabetes and on the seventh day after intravenous injection of siRNAs.
Results: The aortas of diabetic rats demonstrated depressed endothelium-dependent relaxation and integral SMCs outward K+ currents as compared with those of controls. On the seventh day, PKC-δ gene silencing effectively restored K+ currents and increased the amplitude of vascular relaxation up to control levels. An increased level of PKC-δ mRNA in diabetic aortas appeared to be reduced after targeted PKC-δ gene silencing. Similarly, the level of ROS production that was increased in diabetes came back to control values after siRNAs administration.
Conclusions: The silencing of PKC-δ gene expression using siRNAs led to restoration of vasodilator potential in rats with diabetes mellitus. It is likely that the siRNA technique can be a good therapeutic tool to normalize vascular function in diabetes.
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©2014 by De Gruyter
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Articles in the same Issue
- Frontmatter
- Editorial
- Get more of the Journal of Basic and Clinical Physiology and Pharmacology
- Review
- Review on treatment of premenstrual syndrome: from conventional to alternative approach
- Genotoxicity and Cytotoxicity
- Sodium valproate, a histone deacetylase inhibitor ameliorates cyclophosphamide-induced genotoxicity and cytotoxicity in the colon of mice
- Vascular Conditions
- PKC-δ isozyme gene silencing restores vascular function in diabetic rats
- Association of diet and anthropometric measures as cardiovascular modifiable risk factors in young adults
- Assessment of raloxifene, estradiol-17β, dl-ormeloxifene and levormeloxifene on thrombin activity
- Inflammation
- Antibacterial activity of the body wall extracts of sea cucumber (Invertebrata; Echinodermata) on infectious oral streptococci
- Chronic ethanol use in alcoholic beverages by HIV-infected patients affects the therapeutic window of stavudine, lamivudine and nevirapine during the 9-month follow-up period: using chronic alcohol-use biomarkers
- Preclinical efficacy of melatonin in the amelioration of tenofovir nephrotoxicity by the attenuation of oxidative stress, nitrosative stress and inflammation in rats
- Infection
- Antinociceptive and antiedematogenic effect of pecan (Carya illinoensis) nut shell extract in mice: a possible beneficial use for a by-product of the nut industry
- Phytotherapy
- Toxicological evaluation of the lyophilized fruit juice extract of Annona muricata Linn. (Annonaceae) in rodents
- Analgesic, anti-inflammatory and antipyretic effects of Ixora coccinea
- Antidepressant, anxiolytic, and anticataleptic effects of aqueous leaf extract of Antiaris toxicaria Lesch. (Moraceae) in mice: possible mechanisms of actions
- Pharmacological evaluation of the analgesic and anxiolytic activities of Jobelyn® in mice
- Abortifacient potential of ethanolic seed extract of Caesalpinia bonducella in female albino rats
