Inhibitory effects of crocetin on high glucose-induced apoptosis in cultured human umbilical vein endothelial cells and its mechanism.
Dysfunction of endothelial cell is considered as a major cause of vascular complications in diabetes. Crocetin has been shown to have strong antioxidant activities. In present study, we tested whether crocetin inhibited high glucose-induced apoptosis in cultured human umbilical vein endothelial cells (HUVECs) and to explore its possible mechanism. Exposure to high glucose (33 mM) for 72h induced a pronounced increase in apoptosis compared with normal glucose (5.5 mM), as evaluated by cell chromatin staining with Hoechst 33,258 and cell death detection ELISA. High glucose attenuated activation of Akt and endothelial nitric oxide synthase (eNOS). Crocetin (0.1 microM, 1.0 microM) prevented high glucose-induced apoptosis, which correlates with the increase of activation of p-Akt, following the up-regulation of eNOS and NO production. Pretreatment with phosphatidylinositol 3' kinase (Pl3K) inhibitor LY294002 or eNOS inhibitor NG-nitro-arginine methyl ester (LN or L-NAME) inhibited crocetin effect on p-Akt or eNOS, respectively. For the first time, results of our study suggest that crocetin inhibits high glucose-induced apoptosis, at least partly, via Pl3K/Akt/eNOS pathway in HUVECs and crocetin may exert a beneficial effect in preventing diabetes-associated cardiovascular complications.
Meng
Lingdong
L
School of Medicine, Shandong University, Ji'nan 250012, China.
Cui
Lianqun
L
D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002338:Carotenoids / Q000494:pharmacology*; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D009025:Morpholines / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014471:Umbilical Veins / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D014801:Vitamin A / Q000031:analogs & derivatives
D000975:Antioxidants; D002338:Carotenoids; D002867:Chromones; D005947:Glucose; D009025:Morpholines; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D017382:Reactive Oxygen Species; D014801:Vitamin A; C487773:trans-sodium crocetinate; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C496314:NOS3 protein, human