Clearance kinetics of the VGF-derived neuropeptide TLQP-21

Sahu, Bhavani S.; He, Rongjun; Finan, Brian; Cero, Cheryl; Verardi, Raffaello; Razzoli, Maria; Veglia, Gianluigi; Marchi, Richard D. Di; Miles, John M.; Bartolomucci, Alessandro

doi:10.1016/j.npep.2018.06.003

Cited by 19 publications

(22 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Administration of a loading dose of unlabeled peptide caused a slight decrease of the radiolabeled probe only in stomach and intestine. These findings are consistent with the reported expression of TLQP-21 specific binding sites in intestine and stomach and the whole body organ distribution reported for [ 125 I]TLQP-21 ( Guo et al, 2018 ).…”

Section: Discussionsupporting

confidence: 92%

“…injection, [ 18 F]JMV5763 initially accumulated in regions expressing TLQP-21 binding sites such as stomach, intestine, and adrenal gland, but also in lungs. In brain regions the radioactivity remained very low at all times, similarly to results reported with iodinated TLQP-21 ( Guo et al, 2018 ). This suggests low penetrability of [ 18 F]JMV5763 through the BBB, or a very rapid washout from this district.…”

Section: Discussionsupporting

confidence: 85%

“…The complement 3a receptor 1 (C3aR1) and/or the C1q receptor (gC1qR; Chen et al, 2013 ; Hannedouche et al, 2013 ) have been proposed to bind TLQP-21, but this mechanism of action is still matter of debate ( Severini et al, 2008 ). The effects of TLQP-21 have been studied after both central and peripheral administration ( Salton et al, 2000 ; Severini et al, 2009 ; Possenti et al, 2012 ); however, its tissue distribution after systemic administration is poorly known, although more information about its kinetic in plasma have been very recently obtained ( Guo et al, 2018 ) by radiolabeling TLQP-21 with the radionuclide iodine-125, which prompt for a fast initial plasma clearance and a significant long-term uptake in adipose tissue. To obtain a better understanding about the in vivo kinetics of TLQP-21 and its potential target tissues, we have radiolabeled with fluorine-18 a short analog of TLQP-21, namely, JMV5763, that include the 13 aa residues of the C-terminal region of TLQP-21, and retain the capability to fully stimulate intracellular calcium release in CHO cells ( Molteni et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Study of the Tissue Distribution of TLQP-21 in Mice Using [18F]JMV5763, a Radiolabeled Analog Prepared via [18F]Aluminum Fluoride Chelation Chemistry

et al. 2018

View full text Add to dashboard Cite

TLQP-21 is a neuropeptide that is involved in the control of several physiological functions, including energy homeostasis. Since TLQP-21 could oppose the early phase of diet-induced obesity, it has raised a huge interest, but very little is known about its mechanisms of action on peripheral tissues. Our aim was to investigate TLQP-21 distribution in brain and peripheral tissues after systemic administration using positron emission tomography. We report here the radiolabeling of NODA-methyl phenylacetic acid (MPAA) functionalized JMV5763, a short analog of TLQP-21, with [18F]aluminum fluoride. Labeling of JMV5763 was initially performed manually, on a small scale, and then optimized and implemented on a fully automated radiosynthesis system. In the first experiment, mice were injected in the tail vein with [18F]JMV5763, and central and peripheral tissues were collected 13, 30, and 60 min after injection. Significant uptake of [18F]JMV5763 was found in stomach, intestine, kidney, liver, and adrenal gland. In the CNS, very low uptake values were measured in all tested areas, suggesting that the tracer does not efficiently cross the blood–brain barrier. Pretreatment with non-radioactive JMV5763 caused a significant reduction of tracer uptake only in stomach and intestine. In the second experiment, PET analysis was performed in vivo 10–120 min after i.v. [18F]JMV5763 administration. Results were consistent with those of the ex vivo determinations. PET images showed a progressive increase of [18F]JMV5763 uptake in intestine and stomach reaching a peak at 30 min, and decreasing at 120 min. Our results demonstrate that 18F-labeling of TLQP-21 analogs is a suitable method to study its distribution in the body.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 85%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Study of the Tissue Distribution of TLQP-21 in Mice Using [18F]JMV5763, a Radiolabeled Analog Prepared via [18F]Aluminum Fluoride Chelation Chemistry

et al. 2018

View full text Add to dashboard Cite

show abstract

“…5B). Interestingly, tissue distribution studies in mice have shown that intravenously injected TLQP-21 markedly accumulates in the kidney (37). This prompted us to carry out in vivo 'addback' experiments to determine if the TLQP-21 administration can reverse the aggravated renal impairment phenotype observed in the Vgf PT-/mice.…”

Section: Vgf-associated Tlqp-21 Peptide Protects Rtecs Under Stress Cmentioning

confidence: 99%

SOX9 promotes stress-responsive transcription of VGF nerve growth factor inducible gene in kidney epithelial cells

Kim¹,

Bai²,

Jayne³

et al. 2020

Preprint

View full text Add to dashboard Cite

AbstractAcute kidney injury (AKI) is a common clinical condition associated with diverse etiologies and abrupt loss of renal function. In patients with sepsis, rhabdomyolysis, cancer, as well as cardiovascular disorders, the underlying disease or associated therapeutic interventions can cause hypoxic, cytotoxic, and inflammatory insults to renal tubular epithelial cells (RTECs) resulting in the onset of AKI. To uncover stress-responsive disease-modifying genes, here we have carried out renal transcriptome profiling in three distinct murine models of AKI. We find that Vgf nerve growth factor inducible gene upregulation is a common transcriptional stress response in RTECs to ischemia, cisplatin, and rhabdomyolysis-associated renal injury. The Vgf gene encodes a secretory peptide precursor protein that has critical neuro-endocrine functions; however, its role in the kidneys remains unknown. Our functional studies show that RTEC-specific Vgf gene ablation exacerbates ischemia, cisplatin, and rhabdomyolysis-associated AKI in vivo and cisplatin-induced RTEC cell death in vitro. Importantly, addback experiments showed that aggravation of cisplatin-induced renal injury caused by Vgf gene ablation is partly reversed by TLQP-21, a Vgf-derived peptide. Finally, in vitro and in vivo mechanistic studies showed that injury-induced Vgf upregulation in RTECs is driven by the transcriptional regulator Sox9. These findings reveal a crucial downstream target of the Sox9-directed transcriptional program and identify Vgf as a stress-responsive protective gene in kidney epithelial cells.

show abstract

“…Despite the half-life after a single i.v. injection is initially of 0.97 min, the complete terminal value is about 110 min due to tissue uptake and renal clearance [24]. Parenteral or intra-cerebro-ventricular (i.c.v.)…”

Section: Tlqp-21: Endocrine Activitiesmentioning

confidence: 99%

TLQP-21, A VGF-Derived Peptide Endowed of Endocrine and Extraendocrine Properties: Focus on In Vitro Calcium Signaling

Bresciani

Possenti

Coco

et al. 2019

IJMS

View full text Add to dashboard Cite

VGF gene encodes for a neuropeptide precursor of 68 kDa composed by 615 (human) and 617 (rat, mice) residues, expressed prevalently in the central nervous system (CNS), but also in the peripheral nervous system (PNS) and in various endocrine cells. This precursor undergoes proteolytic cleavage, generating a family of peptides different in length and biological activity. Among them, TLQP-21, a peptide of 21 amino acids, has been widely investigated for its relevant endocrine and extraendocrine activities. The complement complement C3a receptor-1 (C3aR1) has been suggested as the TLQP-21 receptor and, in different cell lines, its activation by TLQP-21 induces an increase of intracellular Ca2+. This effect relies both on Ca2+ release from the endoplasmic reticulum (ER) and extracellular Ca2+ entry. The latter depends on stromal interaction molecules (STIM)-Orai1 interaction or transient receptor potential channel (TRPC) involvement. After Ca2+ entry, the activation of outward K+-Ca2+-dependent currents, mainly the KCa3.1 currents, provides a membrane polarizing influence which offset the depolarizing action of Ca2+ elevation and indirectly maintains the driving force for optimal Ca2+ increase in the cytosol. In this review, we address the main endocrine and extraendocrine actions displayed by TLQP-21, highlighting recent findings on its mechanism of action and its potential in different pathological conditions.

show abstract

Clearance kinetics of the VGF-derived neuropeptide TLQP-21

Cited by 19 publications

References 44 publications

Study of the Tissue Distribution of TLQP-21 in Mice Using [18F]JMV5763, a Radiolabeled Analog Prepared via [18F]Aluminum Fluoride Chelation Chemistry

Study of the Tissue Distribution of TLQP-21 in Mice Using [18F]JMV5763, a Radiolabeled Analog Prepared via [18F]Aluminum Fluoride Chelation Chemistry

SOX9 promotes stress-responsive transcription of VGF nerve growth factor inducible gene in kidney epithelial cells

TLQP-21, A VGF-Derived Peptide Endowed of Endocrine and Extraendocrine Properties: Focus on In Vitro Calcium Signaling

Contact Info

Product

Resources

About