Table 1.
Cell type | Treatment | Conc.⁎ (μmol/L) | Time | Main findings | References |
---|---|---|---|---|---|
RTK and MAPK activation | |||||
HEC | HNE | 0.1 | 3 h | HNE (0.1 µM) and oxLDL (200 µg/ml)↑EGFR activation | [36] |
oxLDL | [49] | ||||
BLMVEC | HNE | 10–100 | 2 h | ↑Phosphorylation of ERK, JNK, p38 MAPK | |
MPEC | HNE | 20 | 0–2 h | ↑p∼JNK within 30 min,↔p∼p38, p∼ERK1/2 | [20] |
BLMVEC | HNE | 25 | 30 min | ↑MAPK activation | [88] |
BPAEC | HNE | 50 | 30 min | ↑Phospholipase D activation via protein tyrosine phosphorylation | [37,141] |
HUVEC | 15d-PGJ2 | 10 | 2 h | ↑Phosphorylation of MAPK JNK (2 h) | [142] |
Transcriptional activity | |||||
HUVEC | HNE | 5 | 12 h | ↑HO-1 and NQO1 via Nrf2, protects HUVEC from tBHP attack | [55] |
HUVEC | HNE | 1–10 | 12 h | ↔NFκB activation, ↓IL-8 and ICAM-1 production in a concentration dependent manner indicating ↓inflammatory responses | [10] |
HUVEC | 15d-PGJ2 | 2.5 | 2–8 h | ↑Nrf2 nuclear accumulation, ↑HO-1, ↑NQO1, ↑adducts with Keap1 at cysteines residues in IVR region, which may mediate shear induced Nrf2 activation | [143] |
BAEC | 15d-PGJ2 | 2 | 16 h | ↑GSH, HO-1, ↑Keap1 adduct formation | [144] |
HUVEC | 15d-PGJ2 | 5 | 24 h | ↑GSH, ↑GCLC, ↑GCLM, ↑resistance to oxidative stress which relies on de novo GSH synthesis, ARE responsible for GCLC induction, Cys273 and Cys278 of Keap1 conjugated by 15d-PGJ2 | [52,145] |
Oxidative stress and protein adduct clearance | |||||
BAEC | HNE | 5 | 1 h | Modifies thioredoxin-1 at cys-73 and ↓activity, ↑ROS, ↓GSH | [90] |
HAEC | HNE | 5 | 24 h | Protects HAEC from 6-hydroxydopamine induced cell death | |
BAEC | HNE | 25 | 4 h | Proposed ↑proteasomal degradation of GTPCH and Hsp90 | [23] |
Cellular dysfunction | |||||
BLMVEC | HNE | 10–100 | 2 h | ↑Endothelial permeability; ↑Michael adducts formation, actin fiber remodeling via phosphorylation of ERK, JNK, p38 MAPK | [49] |
BLMVEC | HNE | 25 | 30 min | Induces actin rearrangement, ↓GSH, ↑cell adhesion and surface integrins; ↓tyrosine phosphorylation of FAK,↑MAPK activation, ↑Michael adducts with ↑focal adhesion & adherens junctional proteins, reversed by pretreatment NAC | [88] |
BAEC | HNE | 5 | 1 h | ↑Monocyte adhesion | [90] |
BAEC | HNE | 10 | 5 d | ↑Membrane phospholipid perturbation, ↑prostacyclin, ↑monocyte migration | [146] |
BAEC | HNE | 10 | 6–8 h | ↓Junctional communication | [87] |
BAEC | HNE | 25 | 4 h | ↑ROS, ↓NO, GSH, ↑apoptosis involving caspase-3 activation which can be attenuated by BH4 supplementation. ↓BH4 by ↓GTPCH leading to ↑eNOS uncoupling, ↓HSP90 leading to ↓eNOS phosphorylation, proposed ↑proteasomal activity and proteasomal degradation of BH4 and HSP 90 | [23] |
Mitochondrial function | |||||
BAEC | HNE | 5–10 | 4–16 h | ↑GSH and HO-1 at 16 h, ↑ROS from mitochondria after 4 h | [71] |
HUVEC | 15d-PGJ2 | 2.5 | 24 h | ↑GSH, ↑complex I activity in cell extracts, dependent on de novo protein synthesis in response to ROS but independent of GSH depletion | [94] |
BAEC | 15d-PGJ2 | 10 | 16 h | ↑HO-1, ↓mitochondrial membrane potential ↑Nrf2 nuclear accumulation, blocked IBTP, a mitochondrial-targeted thiol reactive compound. | [53] |
ER stress | |||||
HUVEC | HNE | 25 | 30 min – 2 h | ↑Protein adduction (HSP90, HSP70,PDI), ↑xBP-1 splicing, ↑PERK, p∼eIF2α, and ATF6 translocation; ↑Grp78 and HERP, ↑ICAM-1, cell adhesion, TNF-α, IL-6, and IL-8; activation of endothelial cells mediated by ↑ER stress, noting depletion of GSH cannot ↑ER stress | [107] |
HMEC | HNE | 20 | 24 h | ↑PERK and ATF6; ↑p∼IRE1 and p∼eIF2α; ↑ER stress, which is prevented by pretreatment with NAC | [108] |
HMEC | HNE/oxLDL | 0–25 (HNE)/ 200 µg/ml oxLDL | 14–18 h | Forms adducts with PDI,↓PDI activity and↓cell viability. ↑CHOP and xBP1s mRNA as indicators of ↑ER stress. Loss of PDI activity and reduced viability prevented by NAC. | [110] |
Apoptosis | |||||
HUVEC | HNE | 10–50 | 3 h | ↑Cell death and ↓growth capacity but this effect is affected by serum in the medium | [147] |
HUVEC | HNE | 10 | 12 h | ↑Apoptosis, ↓protein synthesis | [10] |
PCEC | HNE | 1–50 | 3 h | ↑Chromosomal aberrations and micronuclei formation | [113] |
BAEC | HNE | 25 | 4 h | ↑ROS, ↓NO,↓GSH, ↑apoptosis involving caspase-3 activation which can be attenuated by BH4 supplementation. | [23] |
↓BH4 resulting from ↓GTPCH and ↓HSP90 levels leads to ↑eNOS uncoupling and ↓eNOS phosphorylation. Proposed ↑proteasomal activity towards GTPCH and HSP 90 underlies impaired NO production | |||||
MPEC | HNE | 40 | 8 h | ↑p∼JNK leading to ↑p53 and Bax expression and↑apoptosis. Abolished by GST4 overexpression | [20] |
HUVEC | 15d-PGJ2 | 10 | 2–16 h | ↑ROS (1 h), ↑phosphorylation of MAPK and JNK (2 h), ↑p53 expression and phosphorylation (8 h), ↑caspase associated apoptosis | [142] |
Cell type abbreviations: MPEC, mouse pancreatic islet endothelial cells; HEC human endothelial cell line CRL-1998; BAEC, bovine aortic endothelial cells; BLMVEC, Bovine lung microvascular vein endothelial cells; BPAEC, bovine pulmonary arterial endothelial cells; HMEC, human microvascular endothelial cells; HUVEC, human umbilical vein endothelial cells; PCEC, porcine cerebral endothelial cells.