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-κB axis

Rabie, Mostafa A.; Fattah, Mai A. Abd El; Nassar, Noha N.; El‐Abhar, Hanan S.; Abdallah, Dalaal M.

doi:10.1016/j.bcp.2018.01.047

Cited by 71 publications

(45 citation statements)

References 61 publications

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“…Although Ang-(1-7) abolished the myostatin-induced NF-κB signaling activation, the mechanism has not been studied, and more analyses must be performed in order to elucidate it. In this line, the anti-NF-κB activity of Ang-(1-7) has been described in several tissues other than skeletal muscle as a counterregulatory effect to the Ang-II dependent NF-κB activation [50][51][52]. The relevance of the anti-atrophic effect of Ang-(1-7) and especially the depletion of NF-κB signaling has been discussed.…”

Section: Discussionmentioning

confidence: 99%

Angiotensin (1-7) Decreases Myostatin-Induced NF-κB Signaling and Skeletal Muscle Atrophy

Aravena

Ábrigo

González

et al. 2020

IJMS

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Myostatin is a myokine that regulates muscle function and mass, producing muscle atrophy. Myostatin induces the degradation of myofibrillar proteins, such as myosin heavy chain or troponin. The main pathway that mediates protein degradation during muscle atrophy is the ubiquitin proteasome system, by increasing the expression of atrogin-1 and MuRF-1. In addition, myostatin activates the NF-κB signaling pathway. Renin-angiotensin system (RAS) also regulates muscle mass. Angiotensin (1-7) (Ang-(1-7)) has anti-atrophic properties in skeletal muscle. In this paper, we evaluated the effect of Ang-(1-7) on muscle atrophy and signaling induced by myostatin. The results show that Ang-(1-7) prevented the decrease of the myotube diameter and myofibrillar protein levels induced by myostatin. Ang-(1-7) also abolished the increase of myostatin-induced reactive oxygen species production, atrogin-1, MuRF-1, and TNF-α gene expressions and NF-κB signaling activation. Ang-(1-7) inhibited the activity mediated by myostatin through Mas receptor, as is demonstrated by the loss of all Ang-(1-7)-induced effects when the Mas receptor antagonist A779 was used. Our results show that the effects of Ang-(1-7) on the myostatin-dependent muscle atrophy and signaling are blocked by MK-2206, an inhibitor of Akt/PKB. Together, these data indicate that Ang-(1-7) inhibited muscle atrophy and signaling induced by myostatin through a mechanism dependent on Mas receptor and Akt/PKB.

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Section: Discussionmentioning

confidence: 99%

Angiotensin (1-7) Decreases Myostatin-Induced NF-κB Signaling and Skeletal Muscle Atrophy

Aravena

Ábrigo

González

et al. 2020

IJMS

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“…Increased TH transcription plays a crucial role in exercise-dependent neuroplasticity. Application of physical exercises causes activation of CREB by different signal transducers, such as MAPKs, CaMK, and N-methyl-D-aspartate receptor (NMDA-R) in both the hippocampal and striatal plasticity [195,196]. An increase in TH enzyme activity, which is involved in the conversion of L-tyrosine to L-DOPA, from which DA is formed, favors the survival of dopaminergic neurons (Figure 4).…”

Section: Possible Mechanisms Underlying the Protective Effect Of Bndfmentioning

confidence: 99%

BDNF as a Promising Therapeutic Agent in Parkinson’s Disease

Pałasz

Wysocka

Gąsiorowska

et al. 2020

IJMS

341

197

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Brain-derived neurotrophic factor (BDNF) promotes neuroprotection and neuroregeneration. In animal models of Parkinson's disease (PD), BDNF enhances the survival of dopaminergic neurons, improves dopaminergic neurotransmission and motor performance. Pharmacological therapies of PD are symptom-targeting, and their effectiveness decreases with the progression of the disease; therefore, new therapeutical approaches are needed. Since, in both PD patients and animal PD models, decreased level of BDNF was found in the nigrostriatal pathway, it has been hypothesized that BDNF may serve as a therapeutic agent. Direct delivery of exogenous BDNF into the patient's brain did not relieve the symptoms of disease, nor did attempts to enhance BDNF expression with gene therapy. Physical training was neuroprotective in animal models of PD. This effect is mediated, at least partly, by BDNF. Animal studies revealed that physical activity increases BDNF and tropomyosin receptor kinase B (TrkB) expression, leading to inhibition of neurodegeneration through induction of transcription factors and expression of genes related to neuronal proliferation, survival, and inflammatory response. This review focuses on the evidence that increasing BDNF level due to gene modulation or physical exercise has a neuroprotective effect and could be considered as adjunctive therapy in PD.

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“…In addition, DIZE upregulates the expression of Ang-(1-7) and provides positive feedback on its MAS receptor. The mechanism underlying the positive feedback of Ang-(1-7) on the MAS receptor is unclear but Ang-(1-7) activation of the MAS receptor through the PI3K/Akt/BDNF pathway has been reported [28]. Further investigations are needed to clarify the mechanism of action and potential therapeutic value of ACE/ Ang1-7/MAS receptor agonists/activators in the treatment of PH.…”

Section: Discussionmentioning

confidence: 99%

The beneficial effects of angiotensin-converting enzyme II (ACE2) activator in pulmonary hypertension secondary to left ventricular dysfunction

Chen¹,

Lin²,

Liu³

et al. 2020

Int. J. Med. Sci.

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Pulmonary hypertension (PH) is a lethal and rapidly progressing disorder if left untreated, but there is still no definitive therapy. An imbalance between vasoconstriction and vasodilation has been proposed as the mechanism underlying PH. Among the vasomediators of the pulmonary circulation is the renin-angiotensin system (RAS), the involvement of which in the development of PH has been proposed. Within the RAS, angiotensin-converting enzyme 2 (ACE2), which converts angiotensin (Ang) II into Ang-(1-7), is an important regulator of blood pressure, and has been implicated in cardiovascular disease and PH. In this study, we investigated the effects of the ACE2 activator diminazene aceturate (DIZE) on the development of PH secondary to left ventricular dysfunction. A model of PH secondary to left ventricular dysfunction was established in 6-week-old Wistar rats by ascending aortic banding for 42 days. The hemodynamics and pulmonary expression of ACE, Ang II, ACE2, Ang-(1-7), and the Ang-(1-7) MAS receptor were investigated in the early treatment group, which was administered DIZE (15 mg/kg/day) from days 1 to 42, and in the late treatment group, administered DIZE (15 mg/kg/day) from days 29 to 42. Sham-operated rats served as controls. DIZE ameliorated mean pulmonary artery pressure, pulmonary arteriolar remodeling, and plasma brain natriuretic peptide levels, in addition to reversing the overexpression of ACE and up-regulation of both Ang-(1-7) and MAS, in the early and late treatment groups. DIZE has therapeutic potential for preventing the development of PH secondary to left ventricular dysfunction through ACEII activation and the positive feedback of ANG-(1-7) on the MAS receptor. A translational study in humans is needed to substantiate these findings.

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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-κB axis

Cited by 71 publications

References 61 publications

Angiotensin (1-7) Decreases Myostatin-Induced NF-κB Signaling and Skeletal Muscle Atrophy

Angiotensin (1-7) Decreases Myostatin-Induced NF-κB Signaling and Skeletal Muscle Atrophy

BDNF as a Promising Therapeutic Agent in Parkinson’s Disease

The beneficial effects of angiotensin-converting enzyme II (ACE2) activator in pulmonary hypertension secondary to left ventricular dysfunction

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