PMID- 29428223
OWN - NLM
STAT- MEDLINE
DCOM- 20190109
LR  - 20211204
IS  - 1873-2968 (Electronic)
IS  - 0006-2952 (Linking)
VI  - 151
DP  - 2018 May
TI  - Angiotensin 1-7 ameliorates 6-hydroxydopamine lesions in hemiparkinsonian rats 
      through activation of MAS receptor/PI3K/Akt/BDNF pathway and inhibition of 
      angiotensin II type-1 receptor/NF-kappaB axis.
PG  - 126-134
LID - S0006-2952(18)30053-4 [pii]
LID - 10.1016/j.bcp.2018.01.047 [doi]
AB  - MAS receptor (MASR), expressed in several brain areas, conferred neuroprotection 
      against neurodegenerative disorders when activated by angiotensin (Ang) 1-7; 
      however, its role in Parkinson's disease (PD) remains elusive. Intra-striatal 
      post-administration of Ang1-7, using a 6-hydroxydopamine (OHDA) PD model, 
      improved motor performance and muscle coordination. On the molecular level, 
      Ang1-7 upregulated the striatal expression of MASR and caused upsurge in its 
      downstream targets (p-PI3K/p-Akt/p-CREB/BDNF) to phosphorylate TrKB, which in a 
      positive feedback upregulates MASR. Moreover, Ang1-7 increased substantia nigral 
      tyrosine hydroxylase (TH) expression and striatal dopamine (DA) content to 
      indicate the preservation of the dopaminergic neuronal signal. This effect 
      extended to inhibit the striatal expression of Ang II type-1 receptor (AT-1R) to 
      hold the neurodegenerative effect and to boost Ang1-7 
      anti-inflammatory/antioxidant effects by abating NADPH oxidase, along with lipid 
      peroxidation. Indeed, Ang1-7 was able to decrease p-MAPK p38/NF-kappaB p65 to level 
      the inflammatory and oxidative stress events off. The Ang1-7-mediated activation 
      of MASR cue and the suppression of the AT-1R cascade were partially reversed by 
      the intrastartial injection of A-779, a MASR antagonist. The current data 
      suggests a novel therapeutic potential for the Ang1-7 against neurotoxicity 
      associated motor impairment related to PD. The anti-parkinsonian effect of 
      Ang1-7, is in part, mediated by its binding to MASR and the initiation of 
      PI3K/Akt/CREB/BDNF/TrKB cue to increase DA synthesis, besides the 
      downregulation/inhibition of AT-1R/MAPK p38/NF-kappaB p65/NADPH oxidase pathway.
CI  - Copyright (c) 2018 Elsevier Inc. All rights reserved.
FAU - Rabie, Mostafa A
AU  - Rabie MA
AD  - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, 
      Kappaasr El-Aini Str., 11562 Cairo, Egypt.
FAU - Abd El Fattah, Mai A
AU  - Abd El Fattah MA
AD  - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, 
      Kappaasr El-Aini Str., 11562 Cairo, Egypt.
FAU - Nassar, Noha N
AU  - Nassar NN
AD  - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, 
      Kappaasr El-Aini Str., 11562 Cairo, Egypt.
FAU - El-Abhar, Hanan S
AU  - El-Abhar HS
AD  - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, 
      Kappaasr El-Aini Str., 11562 Cairo, Egypt. Electronic address: 
      hanan.elabhar@pharma.cu.edu.eg.
FAU - Abdallah, Dalaal M
AU  - Abdallah DM
AD  - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, 
      Kappaasr El-Aini Str., 11562 Cairo, Egypt.
LA  - eng
PT  - Journal Article
DEP - 20180208
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (NF-kappa B)
RN  - 0 (Peptide Fragments)
RN  - 0 (Proto-Oncogene Mas)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Receptor, Angiotensin, Type 1)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - 8HW4YBZ748 (Oxidopamine)
RN  - 9041-90-1 (Angiotensin I)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - IJ3FUK8MOF (angiotensin I (1-7))
SB  - IM
MH  - Angiotensin I/*pharmacology
MH  - Animals
MH  - Behavior, Animal/drug effects
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Corpus Striatum/drug effects/metabolism
MH  - Male
MH  - NF-kappa B/*metabolism
MH  - Oxidopamine
MH  - Parkinsonian Disorders/*drug therapy/metabolism
MH  - Peptide Fragments/*pharmacology
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Proto-Oncogene Mas
MH  - Proto-Oncogene Proteins/*metabolism
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Rats, Wistar
MH  - Receptor, Angiotensin, Type 1/*metabolism
MH  - Receptors, G-Protein-Coupled/*metabolism
MH  - Signal Transduction/drug effects
OTO - NOTNLM
OT  - A-779
OT  - Dopamine
OT  - NADPH oxidase
OT  - Neuroinflammation
OT  - Tyrosine hydroxylase
EDAT- 2018/02/13 06:00
MHDA- 2019/01/10 06:00
CRDT- 2018/02/12 06:00
PHST- 2017/12/26 00:00 [received]
PHST- 2018/01/30 00:00 [accepted]
PHST- 2018/02/13 06:00 [pubmed]
PHST- 2019/01/10 06:00 [medline]
PHST- 2018/02/12 06:00 [entrez]
AID - S0006-2952(18)30053-4 [pii]
AID - 10.1016/j.bcp.2018.01.047 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 2018 May;151:126-134. doi: 10.1016/j.bcp.2018.01.047. Epub 
      2018 Feb 8.