Glutamine treatment attenuates hyperglycemia-induced mitochondrial stress and apoptosis in umbilical vein endothelial cells

Abstract

OBJECTIVE:The aim of this study was to determine the in vitro effect of glutamine and insulin on apoptosis, mitochondrial membrane potential, cell permeability, and inflammatory cytokines in hyperglycemic umbilical vein endothelial cells.MATERIALS AND METHODS:Human umbilical vein endothelial cells were grown and subjected to glutamine and insulin to examine the effects of these agents on the hyperglycemic state. Mitochondrial function and the production of inflammatory cytokines were assessed using fluorescence analysis and multiple cytotoxicity assays. Apoptosis was analyzed by the terminal deoxynucleotidyl transferase dUTP nick end-labeling assay.RESULTS:Glutamine maintains the integrity of the mitochondria by reducing the cell permeability and cytochrome c levels and increasing the mitochondrial membrane potential. The cytochrome c level was significantly (p<0.005) reduced when the cells were treated with glutamine. An apoptosis assay revealed significantly reduced apoptosis (p<0.005) in the glutamine-treated cells. Moreover, glutamine alone or in combination with insulin modulated inflammatory cytokine levels. Interleukin-10, interleukin-6, and vascular endothelial growth factor were up-regulated while tumor necrosis factor-α was down-regulated after treatment with glutamine.CONCLUSIONS:Glutamine, either alone or in combination with insulin, can positively modulate the mitochondrial stress and cell permeability in umbilical vein endothelial cells. Glutamine regulates the expression of inflammatory cytokines and maintains the balance of the mitochondria in a cytoprotective manner.

Comparative Study of Morphological Characteristics and Body Composition between Different Team Players from Serbian Junior National League: Soccer, Handball, Basketball and Volleyball

“…Adiponectin has antidiabetic, anti-inflammatory and anti-atherogenic properties (Silva et al, 2016). Interleukin 6 acts as a proinflammatory and antinflammatory cytokine (Marginean et al, 2013;Safil et al, 2015), helps regulate responses to the trauma, especially burns and other damaged tissues that lead to inflammation, and it is necessary for resistance against Streptococcus pneumoniae. His lack would weaken the organism (Fischer, 2006).…”

Physalis alkekengi L. Extract Reduces the Oxidative Stress, Inflammation and Apoptosis in Endothelial Vascular Cells Exposed to Hyperglycemia

“…Both pathways lead to DNA fragmentation, the alteration of cytoskeleton and finally the formation of apoptotic bodies. It is known that, in HUVECs, hyperglycemia initiates apoptosis by intrinsic signals [ 67 ], which involves the release from the mitochondria of apoptogenic factors such as cytochrome c and leads to the caspase’s activation, morphological and biochemical changes and cell death [ 68 ]. Growth factors, DNA damage, intracellular Ca 2+ and oxidative stress are the main triggers for the intrinsic pathway [ 69 , 70 ].…”

Effect of rosuvastatin on high glucose-induced endoplasmic reticulum stress in human umbilical vein endothelial cells

“…A considerable number of studies have demonstrated that HG levels lead to endothelial cell dysfunction (Haffner, 2006;Funk et al, 2012), which is thought to be the first step in atherosclerotic plaque formation (Ruggiero et al, 2013;Bruno et al, 2014;Chistiakov et al, 2015), a process involving a series of molecular mechanisms, including activation of oxidative stress, PKC signaling, and ER stress (Mah and Bruno, 2012;Kemeny et al, 2013;Safi et al, 2015). In terms of biological characteristics, HUVECs are similar to artery endothelial cells, and have been widely used as a model to study endothelial cell function (Park et al, 2006).…”

“…Research involving both animal models and patients has demonstrated a correlation between hyperglycemia and endothelial cell dysfunction (Mah and Bruno, 2012). Endothelial cells cultured in high glucose (HG) medium exhibit reduced nitric oxide production (Kemeny et al, 2013) and enhanced expression of inflammation-related genes (Safi et al, 2015). The mechanisms responsible may include accumulation of advanced glycation end products (Janket et al, 2008), increased reactive oxygen species (ROS) production (Cifarelli et al, 2011), activation of protein kinase C (PKC) signaling (Batchuluun et al, 2014), and endoplasmic reticulum (ER) stress (Schisano et al, 2012).…”