title: Blackberry, raspberry and black raspberry polyphenol extracts attenuate angiotensin II-induced senescence in vascular smooth muscle cells.
abstract: Activation of angiotensin II (Ang II) signaling during aging increases reactive oxygen species (ROS) leading to vascular senescence, a process linked to the onset and progression of cardiovascular diseases (CVD). Consumption of fruits and vegetables, particularly berries, is associated with decreased incidence of CVD, which has mainly been attributed to the polyphenol content of these foods. Thus, the objective of this study was to investigate the role of blackberry (BL), raspberry (RB), and black raspberry (BRB) polyphenol extracts in attenuating Ang II-induced senescence in vascular smooth muscle cells (VSMCs) and to determine the molecular mechanisms involved. BL, RB and BRB polyphenol extracts (200 μg ml-1) attenuated Ang II-induced senescence, denoted by decreased number of cells positive for senescence associated β-galactosidase (SA-β-gal) and down-regulation of p21 and p53 expression, which were associated with decreased ROS levels and Ang II signaling. BL polyphenol extract increased superoxide dismutase (SOD) 1 expression, attenuated the up-regulation of Nox1 expression and the phosphorylation of Akt, p38MAPK and ERK1/2 induced by Ang II, and reduced senescence in response to Nox1 overexpression. In contrast, RB and BRB polyphenol extracts up-regulated the expression of SOD1, SOD2, and glutathione peroxidase 1 (GPx1), but exerted no effect on Nox1 expression nor on senescence induced by Nox1 overexpression. BRB reduced signaling similar to BL, while RB was unable to reduce Akt phosphorylation. Furthermore, we demonstrated that inhibition of Akt, p38MAPK and ERK1/2 as well as down-regulation of Nox1 by siRNA prevented senescence induced by Ang II. Our findings indicate that Ang II-induced senescence is attenuated by BL polyphenols through a Nox1-dependent mechanism and by RB and BRB polyphenols in a Nox1-independent manner, likely by increasing the cellular antioxidant capacity.
authors: Department of Nutrition, Food and Exercise Sciences, Florida State University, Tallahassee, FL 32306, USA. gsalazar@fsu.edu and Department of Dietetics and Nutrition, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
authors: Rafaela G
authors: http://orcid.org/0000-0003-0649-2774
authors: RG
authors: Feresin
authors: Department of Nutrition, Food and Exercise Sciences, Florida State University, Tallahassee, FL 32306, USA. gsalazar@fsu.edu.
authors: Jingwen
authors: J
authors: Huang
authors: Department of Nutrition, Food and Exercise Sciences, Florida State University, Tallahassee, FL 32306, USA. gsalazar@fsu.edu.
authors: DawnKylee S
authors: DS
authors: Klarich
authors: Department of Nutrition, Food and Exercise Sciences, Florida State University, Tallahassee, FL 32306, USA. gsalazar@fsu.edu.
authors: Yitong
authors: Y
authors: Zhao
authors: Department of Nutrition, Food and Exercise Sciences, Florida State University, Tallahassee, FL 32306, USA. gsalazar@fsu.edu and Center for Advancing Exercise and Nutrition Research on Aging (CAENRA), Florida State University, Tallahassee, FL 32306, USA.
authors: Shirin
authors: S
authors: Pourafshar
authors: Department of Nutrition, Food and Exercise Sciences, Florida State University, Tallahassee, FL 32306, USA. gsalazar@fsu.edu and Center for Advancing Exercise and Nutrition Research on Aging (CAENRA), Florida State University, Tallahassee, FL 32306, USA.
authors: Bahram H
authors: BH
authors: Arjmandi
authors: Department of Nutrition, Food and Exercise Sciences, Florida State University, Tallahassee, FL 32306, USA. gsalazar@fsu.edu and Center for Advancing Exercise and Nutrition Research on Aging (CAENRA), Florida State University, Tallahassee, FL 32306, USA.
authors: Gloria
authors: G
authors: Salazar
mesh_terms: D000375:Aging / Q000187:drug effects*; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001011:Aorta; D002478:Cells, Cultured; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D059808:Polyphenols / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D065856:Rubus / Q000737:chemistry*; D015398:Signal Transduction
chemical_list: D010936:Plant Extracts; D059808:Polyphenols; D000804:Angiotensin II