Neuroendocrine regulatory peptide-1 and −2: Novel bioactive peptides processed from VGF

Koji, Takehiko; Nakazato, Masamitsu

doi:10.1007/s00018-009-8796-0

Cited by 26 publications

(14 citation statements)

References 51 publications

(59 reference statements)

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“…VGF peptides are present in endocrine cells early during development and adulthood and VGF increases in hyperplasia and tumors [41]. Different peptide fragments have been proposed to derive from VGF, including NAPP, NERP, TLQP, AQEE, and LQEQ [40, 52, 53]. We detected seven peptides of VGF protein, four of them derived from previously described regions: R.LLQQGLAQVEAGR.R (NERP-1), K.NAPPEPVPPPR.A (NAPP-129), R.HHPDLEAQAR.R (TLQP-62/30), and R.SQEEAPGHR.R (APGH).…”

Section: Discussionmentioning

confidence: 99%

“…Remaining three polypeptides (R.SPQPPPPAPAR.D (509–519) , R.ELQETQQER.E (353–661) , and K.LHLPADDVVSIIEEVEEK.R (466–483) ) are derived from regions without known biological activity. Biological roles of VGF-derived peptides like regulation of energy balance, food intake, body fluid homeostasis, and reproduction were described [4, 5, 13, 23, 45, 52]. Clinical and preclinical data links VGF-derived peptides in models of human depression (TLQP 62) [49], neuropathic and inflammatory pain (TLQP 21, AQEE 30) [10, 42], amyotrophic lateral sclerosis, Parkinson’s, and Alzheimer’s diseases [6, 37].…”

Section: Discussionmentioning

confidence: 99%

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Mass spectrometry identification of granins and other proteins secreted by neuroblastoma cells

et al. 2013

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We used mass spectrometry-based protein identification to determine the presence of granins and other proteins in the mouse neuroblastoma secretome. We detected polypeptides derived from four members of the granin family: chromogranin A, chromogranin B, secretogranin III, and VGF. Many of them are derived from previously described biologically active regions; however, for VGF and CgB, we detected peptides not related to known bioactivities. Along with granins, we identified 115 other proteins secreted by mouse neuroblastoma cells, belonging to different functional categories. Fifty-six out of 119 detected proteins possess the signal fragments required for translocation into endoplasmic reticulum. Sequences of remaining 63 proteins were analyzed using SecretomeP algorithm to determine probability of nonclassical secretion. Identified proteins are involved in the regulation of cell cycle, proliferation, apoptosis, angiogenesis, proteolysis, and cell adhesion.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Mass spectrometry identification of granins and other proteins secreted by neuroblastoma cells

et al. 2013

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“…Indeed, to our knowledge, studies on the neurosecretory activity of this family have been limited so far to the demonstration of the ability of NERPs to suppress hypertonic saline-or angiotensin II-induced vasopressin release from hypothalamus and the pituitary (40). In addition, specific analyses have suggested that neither VGF nor TLQP-21 has an impact on the growth hormone-IGF-I axis in pigs or mice (3,32).…”

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confidence: 99%

Characterization of the reproductive effects of the anorexigenic VGF-derived peptide TLQP-21: in vivo and in vitro studies in male rats

Pinilla

Pineda

Gaytán

et al. 2011

American Journal of Physiology-Endocrinology and Metabolism

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VGF (nonacronymic) is a 68-kDa protein encoded by the homonymous gene, which is expressed abundantly at the hypothalamus and has been involved in the control of metabolism and body weight homeostasis. Different active peptide fragments are generated from VGF, including TLQP-21. Circumstantial evidence has suggested that VGF might also participate in the control of reproduction. Yet its mechanisms of action and the eventual role of specific VGF-derived peptides on the hypothalamic-pituitary-gonadal (HPG) axis remain unknown. Herein we report a series of studies on the reproductive effects of TLQP-21 as evaluated in male rats by a combination of in vivo and in vitro analyses. Central administration of TLQP-21 induced acute gonadotropin responses in pubertal and adult male rats, likely via stimulation of GnRH secretion, as documented by static incubations of hypothalamic tissue. In addition, in pubertal (but not adult) males, TLQP-21 stimulated LH secretion directly at the pituitary level. Repeated central administration of TLQP-21 to pubertal males subjected to chronic undernutrition was able to ameliorate the hypogonadotropic state induced by food deprivation. In contrast, chronic administration of TLQP-21 to fed males at puberty resulted in partial desensitization and puberty delay. Finally, in adult (but not pubertal) males, TLQP-21 enhanced hCG-stimulated testosterone secretion by testicular tissue in vitro. In summary, our data are the first to document a complex and multifaceted mode of action of TLQP-21 at different levels of the male HPG axis with predominant stimulatory effects, thus providing a tenable basis for the (direct) reproductive role of this VGF-derived peptide.

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“…The role of the VGF peptides in neurons containing TH, parvoalbumin, GAD and somatostatin remains to be investigated; however the major hypothesized role is that VGF peptides could act as neuromodulators. The VGF role as neuromodulator has already been reported for certain VGF peptides, for instance NERPs regulate vasopressin secretion (Toshinai and Nakazato, 2009; D’Amato et al, 2012), TLQP-21 increases FSH release from the pituitary (Aguilar et al, 2013), TLQP-62 regulates hippocampal synaptic activity (Thakker-Varia et al, 2007, 2010; Bozdagi et al, 2008; Lin et al, 2015). …”

Section: Discussionmentioning

confidence: 89%

Profiles of VGF Peptides in the Rat Brain and Their Modulations after Phencyclidine Treatment

Noli

Sanna

Brancia

et al. 2017

Front. Cell. Neurosci.

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From the VGF precursor protein originate several low molecular weight peptides, whose distribution in the brain and blood circulation is not entirely known. Among the VGF peptides, those containing the N-terminus portion were altered in the cerebro-spinal fluid (CSF) and hypothalamus of schizophrenia patients. “Hence, we aimed to better investigate the involvement of the VGF peptides in schizophrenia by studying their localization in the brain regions relevant for the disease, and revealing their possible modulations in response to certain neuronal alterations occurring in schizophrenia”. We produced antibodies against different VGF peptides encompassing the N-terminus, but also C-terminus-, TLQP-, GGGE- peptide sequences, and the so named NERP-3 and -4. These antibodies were used to carry out specific ELISA and immunolocalization studies while mass spectrometry (MS) analysis was also performed to recognize the intact brain VGF fragments. We used a schizophrenia rat model, in which alterations in the prepulse inhibition (PPI) of the acoustic startle response occurred after PCP treatment. In normal rats, all the VGF peptides studied were distributed in the brain areas examined including hypothalamus, prefrontal cortex, hippocampus, accumbens and amygdaloid nuclei and also in the plasma. By liquid chromatography-high resolution mass, we identified different intact VGF peptide fragments, including those encompassing the N-terminus and the NERPs. PCP treatment caused behavioral changes that closely mimic schizophrenia, estimated by us as a disruption of PPI of the acoustic startle response. The PCP treatment also induced selective changes in the VGF peptide levels within certain brain areas. Indeed, an increase in VGF C-terminus and TLQP peptides was revealed in the prefrontal cortex (p < 0.01) where they were localized within parvoalbumin and tyrosine hydroxylase (TH) containing neurons, respectively. Conversely, in the nucleus accumbens, PCP treatment produced a down-regulation in the levels of VGF C-terminus-, N-terminus- and GGGE- peptides (p < 0.01), expressed in GABAergic- (C-terminus/GGGE) and somatostatin- (N-terminus) neurons. These results confirm that VGF peptides are widely distributed in the brain and modulated in specific areas involved in schizophrenia.

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Neuroendocrine regulatory peptide-1 and −2: Novel bioactive peptides processed from VGF

Cited by 26 publications

References 51 publications

Mass spectrometry identification of granins and other proteins secreted by neuroblastoma cells

Mass spectrometry identification of granins and other proteins secreted by neuroblastoma cells

Characterization of the reproductive effects of the anorexigenic VGF-derived peptide TLQP-21: in vivo and in vitro studies in male rats

Profiles of VGF Peptides in the Rat Brain and Their Modulations after Phencyclidine Treatment

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