Abstract
This study aimed to explore the effect of angiotensin (1-7) (Ang (1-7)) on palmitate-induced apoptosis in islet endothelial cells and the mechanism of action. MS-1 cells were treated with palmitate in the presence or absence of Ang (1-7). The percentage of apoptotic cells was determined by DNA fragmentation and flow cytometry. Reactive oxygen species (ROS) production was measured using a Reactive Oxygen Species Assay Kit. Expression of AKT, eNOS, C-Jun N-terminal kinase (JNK), and p38 was detected by western blotting. Compared with palmitate treated group, palmitate-induced apoptosis was decreased in MS-1 cells which were preincubated with Ang (1-7) (P < 0.05). Palmitate decreased the phosphorylation of AKT and eNOS, and Ang (1-7) increased the phosphorylation of these kinases (P < 0.05), with a concomitant reduction in MS-1 cells apoptosis. Ang (1-7) also inhibited the palmitate-induced ROS production and attenuated the apoptosis-related signaling molecule JNK and p38 activation (all P < 0.05). PI3K/AKT, eNOS, p38 MAPK, and JNK inhibitors blocked the antilipoapoptosis of Ang (1-7) (all P < 0.05). Our findings suggest that Ang (1-7) reduces palmitate-induced islet endothelial cells apoptosis. AKT/eNOS/NO signaling and JNK and p38 pathway are involved in the Ang (1-7)-mediated modulation of islet endothelial cells lipoapoptosis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Angiotensin I / antagonists & inhibitors
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Angiotensin I / pharmacology*
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Angiotensin II / analogs & derivatives
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Angiotensin II / pharmacology
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Animals
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Antihypertensive Agents / antagonists & inhibitors
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Antihypertensive Agents / pharmacology
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Apoptosis / drug effects*
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Cell Line, Transformed
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Endothelium, Vascular / drug effects*
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Endothelium, Vascular / enzymology
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Endothelium, Vascular / metabolism
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Enzyme Activation / drug effects
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Fatty Acids, Nonesterified / antagonists & inhibitors
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Fatty Acids, Nonesterified / metabolism
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Islets of Langerhans / blood supply
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Islets of Langerhans / drug effects*
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Islets of Langerhans / metabolism
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MAP Kinase Kinase 4 / antagonists & inhibitors
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MAP Kinase Kinase 4 / chemistry
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MAP Kinase Kinase 4 / metabolism
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MAP Kinase Signaling System / drug effects*
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Mice
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Microvessels / drug effects
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Microvessels / enzymology
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Microvessels / metabolism
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Nitric Oxide Synthase Type III / antagonists & inhibitors
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Nitric Oxide Synthase Type III / chemistry
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Nitric Oxide Synthase Type III / metabolism*
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Palmitic Acid / antagonists & inhibitors
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Palmitic Acid / metabolism
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Peptide Fragments / antagonists & inhibitors
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Peptide Fragments / pharmacology*
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Protective Agents / chemistry
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Protective Agents / pharmacology
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Protein Kinase Inhibitors / pharmacology
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Proto-Oncogene Mas
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Proto-Oncogene Proteins / agonists
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Proto-Oncogene Proteins / antagonists & inhibitors
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-akt / agonists*
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Proto-Oncogene Proteins c-akt / antagonists & inhibitors
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Proto-Oncogene Proteins c-akt / metabolism
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Receptors, G-Protein-Coupled / agonists
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Receptors, G-Protein-Coupled / antagonists & inhibitors
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Receptors, G-Protein-Coupled / metabolism
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Signal Transduction / drug effects
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p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
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p38 Mitogen-Activated Protein Kinases / chemistry
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p38 Mitogen-Activated Protein Kinases / metabolism
Substances
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7-Ala-angiotensin (1-7)
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Antihypertensive Agents
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Fatty Acids, Nonesterified
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Peptide Fragments
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Protective Agents
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Protein Kinase Inhibitors
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Proto-Oncogene Mas
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Proto-Oncogene Proteins
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Receptors, G-Protein-Coupled
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Angiotensin II
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Palmitic Acid
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Angiotensin I
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Nitric Oxide Synthase Type III
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Nos3 protein, mouse
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Akt1 protein, mouse
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Proto-Oncogene Proteins c-akt
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p38 Mitogen-Activated Protein Kinases
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MAP Kinase Kinase 4
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Map2k4 protein, mouse
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angiotensin I (1-7)