Phoenixin 14 inhibits ischemia/reperfusion-induced cytotoxicity in microglia

Ma, Hongling; Su, Daoqing; Wang, Qingdong; Chong, Zonglei; Zhu, Qiushi; He, Weibin; Wang, Wei

doi:10.1016/j.abb.2020.108411

Cited by 22 publications

(18 citation statements)

References 46 publications

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“…Stein et al, demonstrated that siRNA-downregulated GPR173 mRNA expression attenuated PNX-stimulated LH secretion induced by GnRH in female rats [4]. Consistently, the PNX activation of GPR173 was confirmed in the pituitary cells [4], GnRH-and kisspeptin-positive neurons [29], granulosa cells [20], and murine microglial BV2 cells [30]. GPR173 belongs to the Super Conserved Receptor Expressed in the Brain (SREB) family and is also termed as SREB3.…”

Section: Characterisation Of Phoenixin and Gpr173 Receptormentioning

confidence: 93%

“…In addition, the role of PNX in ischemia/reperfusion (I/R) processes in the heart and in microglial cells of the brain was explored [17,30]. The current available studies on the heart show the highest expression of PNX in the peripheral tissues [3,13].…”

Section: Cell-protective and Anti-inflammatory Effects Of Phoenixinmentioning

confidence: 99%

“…The role of PNX in I/R and ischemic stroke was explored in microglia, and the effects of PNX on cell death and neuronal damage were studied [30]. Oxygen-glucose deprivation/reperfusion leads to acute inflammatory response and increases the secretion of proinflammatory cytokines and reactive oxygen species (ROS) in microglia [69].…”

Section: Cell-protective and Anti-inflammatory Effects Of Phoenixinmentioning

confidence: 99%

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Phoenixin: More than Reproductive Peptide

Billert

Rak

Nowak

et al. 2020

IJMS

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Phoenixin (PNX) neuropeptide is a cleaved product of the Smim20 protein. Its most common isoforms are the 14- and 20-amino acid peptides. The biological functions of PNX are mediated via the activation of the GPR173 receptor. PNX plays an important role in the central nervous system (CNS) and in the female reproductive system where it potentiates LH secretion and controls the estrus cycle. Moreover, it stimulates oocyte maturation and increases the number of ovulated oocytes. Nevertheless, PNX not only regulates the reproduction system but also exerts anxiolytic, anti-inflammatory, and cell-protective effects. Furthermore, it is involved in behavior, food intake, sensory perception, memory, and energy metabolism. Outside the CNS, PNX exerts its effects on the heart, ovaries, adipose tissue, and pancreatic islets. This review presents all the currently available studies demonstrating the pleiotropic effects of PNX.

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Section: Characterisation Of Phoenixin and Gpr173 Receptormentioning

confidence: 93%

Section: Cell-protective and Anti-inflammatory Effects Of Phoenixinmentioning

confidence: 99%

Section: Cell-protective and Anti-inflammatory Effects Of Phoenixinmentioning

confidence: 99%

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Phoenixin: More than Reproductive Peptide

Billert

Rak

Nowak

et al. 2020

IJMS

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“…Studies have shown that myeloid differentiation factor 88 (Myd88) plays a vital role in the development of CIRI [4][5][6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

A self-developed MyD88 inhibitor across the blood-brain barrier fully reverses acute cerebral ischemia-reperfusion injury

Zhao

Zhang

et al. 2022

Preprint

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Background: The acute ischemia-reperfusion injury that occurs after an ischemic stroke is almost inevitable. In treating ischemic stroke, the prevention and treatment of cerebral ischemia-reperfusion injury (CIRI) is an undeniable difficulty clinically. Despite increasing studies being done on the subject, medicines showing effective neurological improvements after reperfusion is still minimal. This study aims to investigate the effects of a self-developed MyD88 inhibitor (TJ-M2010-5) on CIRI and its mechanism.Methods: The middle cerebral artery occlusion (MCAO) model was used to simulate CIRI in mice. BV-2 cells were cultured for the mechanism study by LPS stimulation in vitro. Neurological deficit score and cerebral infarction volume were studied. Immunofluorescence staining was used to measure neuronal damage and apoptosis in the brain. The anti-inflammation effect of TJ-M2010-5 was evaluated by analyzing the expression of inflammatory cytokines, activation of microglia and infiltration of peripheral myeloid cells. The expression of TLR4/Myd88/NF-κB signaling pathway protein was detected by Simple Western. The concentrations of TJ-M2010-5 in blood and brain were analyzed by LC-MS methods.Results: The cerebral infarction volume decreased in mice treated with TJ-M2010-5, with the most prominent decrease in approximately 80% of the original infarction volume. Moreover, the downregulation of apoptosis and NeuN protein expression in the brain of infarction area further indicated that neuronal damage was alleviated. TJ-M2010-5 treatment also reduced the infiltration ratio of peripheral myeloid cells in the cerebral infarction area and increased the proportion of inactive microglia. The inflammatory cytokines decreased after TJ-M2010-5 treatment in infarction area and supernatant. TJ-M2010-5 downregulated the expression of iNOS and inhibited TLR4/MyD88/NF-κB signaling pathway in vivo and in vitro. In addition, TJ-M2010-5 could freely pass through the blood-brain barrier.Conclusions: TJ-M2010-5 has shown to have an excellent therapeutic effect on CIRI by inhibiting TLR4/Myd88/NF-κB signaling pathway to decrease excessive inflammatory response, showing the potential to change the history that there is no effective medicine for the treatment of CIRI. and also has the potential to be utilized in brain neuroinflammatory diseases.

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“…Recently, neuropeptidomic searches in arthropod transcriptomes revealed phoenixin precursors with conserved cleavage sites to produce the mature PNX peptide PNX14 and PNX-20 (Nguyen et al 2018). PNX is involved in many different physiological functions in mammals, such as cardio-modulation, memory, anxiety, food intake and reproduction (Clarke and Dhillo 2019;Schalla and Stengel 2019;Billert et al 2020;Haddock et al 2020;Ma et al 2020;Schalla et al 2020;Friedrich and Stengel 2021;Yao et al 2021). The mechanism of signalling of PNX, an orphan ligand, remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Pre-metazoan origin of neuropeptide signalling

Yáñez-Guerra

Thiel

Jékely

2021

Preprint

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Neuropeptides are a diverse class of signalling molecules in metazoans. They occur in all animals with a nervous system and also in neuron-less placozoans. However, their origin has remained unclear because no neuropeptide shows deep homology across lineages and none have been found in sponges. Here, we identify two neuropeptide precursors, phoenixin and nesfatin, with broad evolutionary conservation. By database searches, sequence alignments and gene-structure comparisons we show that both precursors are present in bilaterians, cnidarians, ctenophores and sponges. We also found phoenixin and a secreted nesfatin precursor homolog in the choanoflagellate Salpingoeca rosetta. Phoenixin in particular, is highly conserved, including its cleavage sites, suggesting that prohormone processing occurs also in choanoflagellates. In addition, based on phyletic patterns and negative pharmacological assays we question the originally proposed GPR-173 (SREB3) as a phoenixin receptor. Our findings indicate that signalling by secreted neuropeptide homologs has pre-metazoan origins and thus evolved before neurons.

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Phoenixin 14 inhibits ischemia/reperfusion-induced cytotoxicity in microglia

Cited by 22 publications

References 46 publications

Phoenixin: More than Reproductive Peptide

Phoenixin: More than Reproductive Peptide

A self-developed MyD88 inhibitor across the blood-brain barrier fully reverses acute cerebral ischemia-reperfusion injury

Pre-metazoan origin of neuropeptide signalling

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