Uric acid can enhance MAPK pathway-mediated proliferation in rat primary vascular smooth muscle cells via controlling of mitochondria and caspase-dependent cell death. (4th May 2022)

• Record Type: Journal Article
• Authors: Doğru, Segün; Yaşar, Ekrem; Yeşilkaya, Akın
• Is Part Of: Journal of receptor and signal transduction research. Volume 42:Number 3(2022)
• Page Start: 293
• Page End: 301
• Publication Date: 2022-05-04
• Subjects: Uric acid -- VSMCs -- proliferation -- MAPKs -- apoptosis; Cell receptors -- Periodicals; Cellular signal transduction -- Periodicals; 571.6
• DOI: 10.1080/10799893.2021.1931320
• Languages: English
• ISSNs: 1079-9893

Abstract

Abstract: Hyperuricemia may be a risk factor for cardiovascular diseases such as hypertension and atherosclerosis, but the mechanisms underlying uric acid-induced pathological conditions remain unknown. In this study, we investigated the effect of short time and long-term administration of increasing uric acid concentrations on cell viability, proliferative and apoptotic pathways in vascular smooth muscle cells (VSMCs). Cell viability/proliferation was determined with WST-1 assay. Expression levels of mitogen-activated protein kinases (MAPKs) (phosphorylated (p)-p38 and p-p44/42 MAPK), extrinsic (caspase 3, caspase 8), and intrinsic (B-cell lymphoma-extra-large (Bcl-xL)) apoptotic pathway proteins were measured by Western blotting. In order to assess the proliferative effects of uric acid incubations on VSMCs, we monitored the proliferative/apoptosis signaling pathways for up to 24 h. Our results indicated that uric acid increases cell viability at time and dose-dependently in VSMCs. Immunoblotting results showed that uric acid treatment elevated the expression level of p-p38 MAPK but did markedly reduce the protein levels of p-p44/42, compared with all the uric acid doses-treated VSMCs, especially at 1 h. Uric acid stimulation increased caspase-3 protein levels and decreased Bcl-xL, but did not alter caspase-8 protein expression at the same dose and time. Furthermore, low uric acid incubations (0–7.5 mg/dL) did not affect any signaling pathways for long time points (6–24 h). In conclusion, our study demonstrates for the first time that VSMCs induced with uric acid can affect cell viability, proliferative, and apoptosis pathways at the widest time and dose range. These findings provide a better understanding of the uric acid effects related to vascular impairments.