PMID- 30135489
OWN - NLM
STAT- MEDLINE
DCOM- 20191126
LR  - 20191126
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 8
IP  - 1
DP  - 2018 Aug 22
TI  - Improvement of vascular dysfunction by argirein through inhibiting endothelial 
      cell apoptosis associated with ET-1/Nox4 signal pathway in diabetic rats.
PG  - 12620
LID - 10.1038/s41598-018-30386-w [doi]
LID - 12620
AB  - Endothelial cell apoptosis plays an important role in the pathophysiological 
      mechanism of vascular complications in type 2 diabetes mellitus (T2DM). Argirein, 
      a new synthetic compound was demonstrated to inactivate NADPH oxidase to 
      alleviate cardiac dysfunction in T2DM. Here, we investigated whether argirein 
      medication attenuated the vascular dysfunction in T2DM by inhibiting endothelial 
      cell apoptosis which was associated with NADPH oxidase. The rat aortic 
      endothelial cells (RAECs) were incubated with glucose (30 mM) for 48 hour in 
      vitro. It was shown that high glucose significantly increased the protein 
      expression of BAX (Bcl-2 Associated X protein) and Caspase-3 and decreased Bcl2 
      (B-Cell Leukemia/Lymphoma 2) protein level in RAECs, which was normalized by 
      argirein medication. The annexin V-FITC bound cell percentage and DNA fragments 
      in agarose electrophoresis were markedly suppressed by argirein to confirm the 
      anti-apoptotic property of argirein in RAECs. Furthermore, we found that argirein 
      blocked the endothelin (ET)-1/Nox4 signal-dependent superoxide (O(2)(-.)) 
      generation, which regulated endothelial cell apoptosis in RAECs. In vivo, 
      argirein intervention relieved the vasodilatory response to acetylcholine and 
      restored the expressions of Nox4 and BAX in the aorta endothelium of high-fat 
      diet (HFD)-fed rats following streptozocin (STZ) injection. For the first time, 
      we demonstrated that argirein could inhibit vascular endothelial cell apoptosis, 
      which was attributed to blocking ET-1/Nox4 signal-dependent O(2)(-) generation in 
      RAECs. This current study revealed the therapeutic effects of argirein to prevent 
      the vascular complication in T2DM through inhibiting endothelial cell apoptosis 
      which was associated with the anti-oxidative property of argirein.
FAU - Su, Jie
AU  - Su J
AD  - Department of Clinical Pharmacy, School of Preclinical Medicine and Clinical 
      Pharmacy, China Pharmaceutical University, Nanjing, 210009, China.
FAU - An, Xing-Rong
AU  - An XR
AD  - Department of Clinical Pharmacy, School of Preclinical Medicine and Clinical 
      Pharmacy, China Pharmaceutical University, Nanjing, 210009, China.
FAU - Li, Qing
AU  - Li Q
AD  - Department of Clinical Pharmacy, School of Preclinical Medicine and Clinical 
      Pharmacy, China Pharmaceutical University, Nanjing, 210009, China.
FAU - Li, Xiao-Xue
AU  - Li XX
AD  - Department of Pathology, Medical School of Southeast University, Nanjing, 210009, 
      China.
FAU - Cong, Xiao-Dong
AU  - Cong XD
AD  - School of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, 311400, China.
FAU - Xu, Ming
AU  - Xu M
AD  - Department of Clinical Pharmacy, School of Preclinical Medicine and Clinical 
      Pharmacy, China Pharmaceutical University, Nanjing, 210009, China. 
      mingxu@cpu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180822
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Anthraquinones)
RN  - 0 (Drug Combinations)
RN  - 0 (Endothelin-1)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (argirein)
RN  - 0 (bcl-2-Associated X Protein)
RN  - 5W494URQ81 (Streptozocin)
RN  - 94ZLA3W45F (Arginine)
RN  - EC 1.6.3.- (NADPH Oxidase 4)
RN  - EC 1.6.3.- (NADPH Oxidases)
RN  - EC 1.6.3.- (Nox4 protein, rat)
RN  - EC 3.4.22.- (Caspase 3)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Anthraquinones/*pharmacology
MH  - Aorta
MH  - Apoptosis/drug effects
MH  - Arginine/*pharmacology
MH  - Caspase 3/metabolism
MH  - Diabetes Mellitus, Experimental/drug therapy/pathology
MH  - Drug Combinations
MH  - Endothelial Cells/drug effects/metabolism
MH  - Endothelin-1/*metabolism
MH  - Endothelium, Vascular/metabolism
MH  - Glucose/metabolism
MH  - Male
MH  - NADPH Oxidase 4/*metabolism
MH  - NADPH Oxidases/drug effects/metabolism
MH  - Proto-Oncogene Proteins c-bcl-2/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reactive Oxygen Species/metabolism
MH  - Signal Transduction/drug effects
MH  - Streptozocin/pharmacology
MH  - bcl-2-Associated X Protein/metabolism
PMC - PMC6105644
COIS- The authors declare no competing interests.
EDAT- 2018/08/24 06:00
MHDA- 2019/11/27 06:00
PMCR- 2018/08/22
CRDT- 2018/08/24 06:00
PHST- 2018/04/17 00:00 [received]
PHST- 2018/07/24 00:00 [accepted]
PHST- 2018/08/24 06:00 [entrez]
PHST- 2018/08/24 06:00 [pubmed]
PHST- 2019/11/27 06:00 [medline]
PHST- 2018/08/22 00:00 [pmc-release]
AID - 10.1038/s41598-018-30386-w [pii]
AID - 30386 [pii]
AID - 10.1038/s41598-018-30386-w [doi]
PST - epublish
SO  - Sci Rep. 2018 Aug 22;8(1):12620. doi: 10.1038/s41598-018-30386-w.