Targeting drugs to APJ receptor: From signaling to pathophysiological effects

Huang, Zhen; He, Lu; Chen, Zhe; Chen, Linxi

doi:10.1002/jcp.27047

Cited by 29 publications

(17 citation statements)

References 105 publications

(191 reference statements)

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“…The APJ receptor, first identified in 1993, is a member of the G protein-coupled receptor family closely related to the angiotensin receptor, but it is not coupled by angiotensin II [85,86]. Only in 1998 was an APJ endogenous ligand found: apelin (APLN) [87].…”

Section: Apelin/apj Axis: Biological Rolementioning

confidence: 99%

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Adipokines, Myokines, and Cardiokines: The Role of Nutritional Interventions

Senesi

Luzi

Terruzzi

2020

IJMS

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: It is now established that adipose tissue, skeletal muscle, and heart are endocrine organs and secrete in normal and in pathological conditions several molecules, called, respectively, adipokines, myokines, and cardiokines. These secretory proteins constitute a closed network that plays a crucial role in obesity and above all in cardiac diseases associated with obesity. In particular, the interaction between adipokines, myokines, and cardiokines is mainly involved in inflammatory and oxidative damage characterized obesity condition. Identifying new therapeutic agents or treatment having a positive action on the expression of these molecules could have a key positive effect on the management of obesity and its cardiac complications. Results from recent studies indicate that several nutritional interventions, including nutraceutical supplements, could represent new therapeutic agents on the adipo-myo-cardiokines network. This review focuses the biological action on the main adipokines, myokines and cardiokines involved in obesity and cardiovascular diseases and describe the principal nutraceutical approaches able to regulate leptin, adiponectin, apelin, irisin, natriuretic peptides, and follistatin-like 1 expression.

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Section: Apelin/apj Axis: Biological Rolementioning

confidence: 99%

“…Recent evidence highlights how APLN has many biological functions and above all plays a crucial role in the cardiovascular and metabolic systems [84,86,88].…”

Section: Apelin/apj Axis: Biological Rolementioning

confidence: 99%

Adipokines, Myokines, and Cardiokines: The Role of Nutritional Interventions

Senesi

Luzi

Terruzzi

2020

IJMS

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“…; Huang et al. ), the podocyte apelinergic system may become a good target for the treatment of DKD.…”

Section: Discussionmentioning

confidence: 99%

“…APJ is a G protein‐coupled receptor consisting of seven transmembrane domains, that shares a 31% identical amino acid sequence with angiotensin AT1 receptor, but does not bind angiotensin II (Ang II) (Huang et al. ). Messenger RNA (mRNA) molecules for preproapelin and APJ are expressed in human tissues such as stomach, brain, heart, kidney, adipose tissue, lung, and in human endothelial cells (Hosoya et al.…”

Section: Introductionmentioning

confidence: 99%

Apelinergic system in the kidney: implications for diabetic kidney disease

et al. 2018

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The bioactive peptides of the apelinergic system and its receptor APJ have been shown to play a protective role in experimental cardiovascular and diabetic kidney disease (DKD). Mechanisms of this renoprotective effect remain to be elucidated. In this study, we examined the localization of APJ within the normal kidney and its kidney expression in the db/db model of DKD. The effect of hyperglycemia and angiotensin II on APJ was examined in cultured podocytes. In the glomerulus, APJ colocalized with podocyte but not endothelial cell markers. In podocytes stimulated with Pyr 1Apelin‐13, a change in the phosphorylation status of the signaling proteins, AKT, ERK, and p70S6K, was observed with an increase 15 min after stimulation. Apelin‐13 decreased activity of Caspase‐3 in podocytes after high glucose treatment reflecting an antiapoptotic effect of APJ stimulation. In podocytes, APJ mRNA was downregulated in high glucose, when compared to normal glucose conditions and exposure to angiotensin II led to a further significant decrease in APJ mRNA. APJ and preproapelin mRNA levels in kidneys from db/db mice were markedly decreased along with decreased tubular APJ protein by western blotting and immunostaining when compared to db/m controls. In conclusion, the apelinergic system is decreased in kidneys from db/db mice. Within the glomerulus, APJ is mainly localized in podocytes and in this cell type its activation by Apelin‐13 abolishes the proapoptotic effect of high glucose, suggesting a potential therapeutic role of apelin and emerging agonists with extended half‐life for therapy of DKD.

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“…APLNR is an orphaned G-protein-coupled receptor (GPCR), which distributed widely throughout the body, including central nervous system, heart, kidney, and other periphery organs [24,25] . According to the reports, APLNR has no other subtypes and has two known ligands: Apelin and Elabela [26] . Previous studies had showed that Apelin had protective effects against oxidative induced injuries.…”

Section: Introductionmentioning

confidence: 99%

Elabela-APLNR Inhibits Cerebral Ischemia/Reperfusion Injury Through AMPK/SIRT3/PGC-1α and Akt/Nrf2 Pathways

Wang

Duan

Huang

et al. 2020

Preprint

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Inhibiting mitochondrial dysfunction and oxidative stress has benefits effects for the treatment of cerebral ischemia/reperfusion injury (CI/RI). Elabela/APLENR system had showed to be protective against ischemia/reperfusion induced injury in other tissue. However, whether Elabela had protective effects against CI/RI and its possible mechanisms were largely unknown. This study was designed to evaluate the effects of Elabela 32 (ELA32) against CI/RI. In vivo, behavioral test, infarct size and brain edema were evaluated on rats middle cerebral artery occlusion/reperfusion (MCAO/R) model after treated by ELA32. In vitro, HT22 cells were subjected to glucose deprivation/reperfusion (OGD/R) and treated with ELA32 in presence of SIRT3-siRNA, or AMPK-siRNA, or Nrf2-siRNA. Cell viability, cell apoptosis, ROS and ATP levels, mitochondrial related proteins and oxidative related cytokines were measured by relative methods.As the results showed, neurological scores, infarct size, brain edema and injury cytokines were improved by ELA32 treatment in rats. Subsequently, we found that ELA32 inhibited cell apoptosis, mitochondrial dysfunction, and oxidative stress in a dose dependent manner in brain and HT22 cell. Western blotting results showed that ELA32 induced the deacetylation and phosphorylation of PGC-1α, the expression of Nrf2, SIRT3 and APLNR, and the phosphorylation of AMPK and Akt. Further, the crosstalk relationship between APLNR, SIRT3, AMPK, PGC-1α, Akt and Nrf2 were verified by the specific targeted siRNA transfection. The same effects on APLNR related pathways were also observed in rats.In conclusion, ELA32 improved mitochondrial dysfunction and oxidative stress through regulating APLNR mediated AMPK/SIRT3/PGC-1α pathway and Akt/Nrf2 pathway. These results indicated that ELA32/APLNR system plays some role in central nervous system, and more studies should be performed to confirm these effects.

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Targeting drugs to APJ receptor: From signaling to pathophysiological effects

Cited by 29 publications

References 105 publications

Adipokines, Myokines, and Cardiokines: The Role of Nutritional Interventions

Adipokines, Myokines, and Cardiokines: The Role of Nutritional Interventions

Apelinergic system in the kidney: implications for diabetic kidney disease

Elabela-APLNR Inhibits Cerebral Ischemia/Reperfusion Injury Through AMPK/SIRT3/PGC-1α and Akt/Nrf2 Pathways

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