L-Theanine Down-Regulates the JAK/STAT3 Pathway to Attenuate the Proliferation and Migration of Vascular Smooth Muscle Cells Induced by Angiotensin II

Biol Pharm Bull. 2018;41(11):1678-1684. doi: 10.1248/bpb.b18-00387.

Abstract

L-Theanine, a green tea amino acid derivative, has cardiovascular qualities. The focus of the current evaluation was to examine the suppression of L-theanine on cultured vascular smooth muscle cell (VSMC) proliferation and migration that is prompted by angiotensin II (Ang II). The VSMCs were treated with non-cytotoxic concentrations of L-theanine and then stimulated with Ang II. The CCK-8 and Transwell chamber assays were monitored on the proliferation and migration rate, respectively. We discovered that L-theanine (50 and 100 µM) significantly halted Ang II-induced VSMC proliferation and migration. This was joined by a decline in the amount of cyclin D1. An additional discovery was that L-theanine lowered the proportion of S-phase cells, whereas the number of G1/G0-phase cells in Ang II-stimulated VSMCs was elevated, based on flow cytometry. Western blotting analyses indicated that L-theanine had no impact on extracellular-signal-regulated kinase 1/2 (ERK1/2) activation prompted by Ang II. Nevertheless, L-theanine significantly lowered Ang II-prompted phosphorylation of Janus kinase 2 (JAK2), c-Src tyrosine kinase, and signal transducer and activators of transcription 3 (STAT3). The outcomes revealed that L-theanine subdued the Ang II-prompted proliferation and migration of VSMC, partly via the obstruction of the JAK/STAT3 pathway instead of via just the ERK pathway.

Keywords: Janus kinase 2 (JAK2); L-theanine; angiotensin II; proliferation; signal transducer and activator of transcription 3 (STAT3); vascular smooth muscle cell.

MeSH terms

  • Angiotensin II / metabolism*
  • Animals
  • CSK Tyrosine-Protein Kinase
  • Camellia sinensis / chemistry*
  • Cell Movement
  • Cell Proliferation
  • Cells, Cultured
  • Down-Regulation
  • Glutamates / pharmacology*
  • Janus Kinase 2 / metabolism*
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / drug effects*
  • Myocytes, Smooth Muscle / drug effects
  • Phosphorylation
  • Plant Extracts / pharmacology*
  • Rats, Sprague-Dawley
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction
  • src-Family Kinases / metabolism

Substances

  • Glutamates
  • Plant Extracts
  • STAT3 Transcription Factor
  • Angiotensin II
  • theanine
  • CSK Tyrosine-Protein Kinase
  • Jak2 protein, rat
  • Janus Kinase 2
  • src-Family Kinases