title: Ang (1-7) protects islet endothelial cells from palmitate-induced apoptosis by AKT, eNOS, p38 MAPK, and JNK pathways.
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.
authors.affiliation: Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yuan
authors.affiliation: Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Chun-Li
authors.initials: CL
authors.lastname: Lu
authors.affiliation: Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Xiao-Ya
authors.initials: XY
authors.lastname: Li
mesh_terms: D000803:Angiotensin I / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000804:Angiotensin II / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002461:Cell Line, Transformed; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005230:Fatty Acids, Nonesterified / Q000037:antagonists & inhibitors / Q000378:metabolism; D007515:Islets of Langerhans / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D048670:MAP Kinase Kinase 4 / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051379:Mice; D055806:Microvessels / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D019308:Palmitic Acid / Q000037:antagonists & inhibitors / Q000378:metabolism; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D020011:Protective Agents / Q000737:chemistry / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism
chemical_list: C092006:7-Ala-angiotensin (1-7); D000959:Antihypertensive Agents; D005230:Fatty Acids, Nonesterified; D010446:Peptide Fragments; D020011:Protective Agents; D047428:Protein Kinase Inhibitors; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; D000804:Angiotensin II; D019308:Palmitic Acid; D000803:Angiotensin I; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; C514862:Akt1 protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; C482562:Map2k4 protein, mouse; C118790:angiotensin I (1-7)