Neuropeptide Y activates phosphorylation of ERK and STAT3 in stromal vascular cells from brown adipose tissue, but fails to affect thermogenic function of brown adipocytes

Shimada, Kohei; Ohno, Yuta; Okamatsu‐Ogura, Yuko; Suzuki, Masahiro; Kamikawa, Akihiro; Terao, Akira; Kimura, Kazuhiro

doi:10.1016/j.peptides.2012.02.012

Cited by 15 publications

(8 citation statements)

References 38 publications

(59 reference statements)

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“…STAT3 phosphorylation at Ser727 residue has been shown to increase the transcriptional potential of STAT3, and the cooperation of both tyrosine (705) as well as serine (727) phosphorylation is necessary for full activation of Stat3 [ 41 , 42 ]. Shimada et al [ 21 ] has showed that NPY increased phosphorylation STAT3 at Ser 727 residue in stromal vascular cells from brown adipose tissue. Transcriptional activation of eukaryotic genes often requires the cooperative action of many proteins [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

“…However, its molecular mechanism has not been fully elucidated. In stromal vascular cells and brain, NPY has been proved to modulate phosphorylation of STAT3 and expression of c-fos [ 20 , 21 ], which are important signaling molecules also involved in VSMC functions [ 22 ]. Since studies have revealed that plasma concentration of NPY is increased during hypertension in pregnancy and NPY is involved in the regulation of VSMC functions, we therefore hypothesized that NPY plays important roles in vascular remodeling during hypertension in pregnancy, which may involve STAT3 and c-fos pathways.…”

Section: Introductionmentioning

confidence: 99%

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Neuropeptide Y Stimulates Proliferation and Migration of Vascular Smooth Muscle Cells from Pregnancy Hypertensive Rats via Y1 and Y5 Receptors

Zhang

Yao

et al. 2015

PLoS ONE

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The increased proliferation and migration of vascular smooth muscle cells (VSMCs) play important roles in pathophysiological remodeling of arteries during hypertension in pregnancy. However, the mechanisms involved in this process remain unclear. We hypothesized that Neuropeptide Y (NPY), which is a potent mitogenic peptide, participates in modulating proliferation and migration of VSMCs during hypertension in pregnancy. Using pregnant hypertensive rats, induced by intraperitoneal injection of L-nitro-arginine methylester (L-NAME), the plasma concentration of NPY was detected. Open angle, which reflects the non-uniform remodeling with high sensitivity, was used to detect the pathophysiological vascular remodeling in vivo. The results revealed that NPY concentration and artery open angle were both significantly increased in rats with hypertension in pregnant. The underlying mechanism of elevated NPY on vascular remodeling were further analyzed by using cultured VSMCs in vitro. In cultured VSMCs, NPY most effectively stimulated the migration and proliferation of VSMCs at 10-6 mol/L, similar to the plasma concentration in L-NAME hypertension in pregnant rats. NPY up-regulated the expressions of both Y1 and Y5 receptors, increased the phosphorylations of STAT3 on Tyr705 and Ser727 residues, and induced the expression of c-Fos. The NPY-induced VSMCs proliferation was reduced by Y5 receptor antagonist, and fully blocked by combinations with other antagonist, such as Y2+Y5, Y1+Y5, and Y1+Y2+Y5. In contrast, the NPY-induced VSMC migration was blocked by either Y receptor antagonist or any combination of Y receptor antagonists. These results suggest that the elevated plasma concentration of NPY during hypertension in pregnancy may induce VSMC proliferation mainly via Y5 receptor, which subsequently modulate STAT3 and c-Fos signaling pathways to result in the vascular remodeling. These results also suggest that NPY mainly acts on VSMCs in vitro via Y1, Y5 receptors and in vascular tissues in vivo via Y5 receptor.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Neuropeptide Y Stimulates Proliferation and Migration of Vascular Smooth Muscle Cells from Pregnancy Hypertensive Rats via Y1 and Y5 Receptors

Zhang

Yao

et al. 2015

PLoS ONE

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“…Oxygen concentration in the chamber was monitored continuously for 5 min before and 10 min after the addition of 1 µM NE. NE concentration necessary to obtain the maximal effect in brown adipocytes was determined as described previously [32]. Oxygen consumption rates were calculated using computer software (782 System; Strathkelvin Instruments, Glasgow, Scotland).…”

Section: Methodsmentioning

confidence: 99%

Thermogenic Ability of Uncoupling Protein 1 in Beige Adipocytes in Mice

et al. 2013

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Chronic adrenergic activation leads to the emergence of beige adipocytes in some depots of white adipose tissue in mice. Despite their morphological similarities to brown adipocytes and their expression of uncoupling protein 1 (UCP1), a thermogenic protein exclusively expressed in brown adipocytes, the beige adipocytes have a gene expression pattern distinct from that of brown adipocytes. However, it is unclear whether the thermogenic function of beige adipocytes is different from that of classical brown adipocytes existing in brown adipose tissue. To examine the thermogenic ability of UCP1 expressed in beige and brown adipocytes, the adipocytes were isolated from the fat depots of C57BL/6J mice housed at 24°C (control group) or 10°C (cold-acclimated group) for 3 weeks. Morphological and gene expression analyses revealed that the adipocytes isolated from brown adipose tissue of both the control and cold-acclimated groups consisted mainly of brown adipocytes. These brown adipocytes contained large amounts of UCP1 and increased their oxygen consumption when stimulated with norepinephirine. Adipocytes isolated from the perigonadal white adipose tissues of both groups and the inguinal white adipose tissue of the control group were white adipocytes that showed no increase in oxygen consumption after norepinephrine stimulation. Adipocytes isolated from the inguinal white adipose tissue of the cold-acclimated group were a mixture of white and beige adipocytes, which expressed UCP1 and increased their oxygen consumption in response to norepinephrine. The UCP1 content and thermogenic ability of beige adipocytes estimated on the basis of their abundance in the cell mixture were similar to those of brown adipocytes. These results revealed that the inducible beige adipocytes have potent thermogenic ability comparable to classical brown adipocytes.

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“…Moreover, given that ERK phosphorylation is reported to be induced by NPY 35 – 38 especially during chemotaxis 39 , 40 and that the intracellular signalling cascade of NPY 12 converging on ERK is also able to amplify growth-promoting effects 34 , we asked if ERK phosphorylation was altered after blocking of NPY. Our data have shown that the blocking of NPY receptors did not alter ERK phosphorylation in ASCs respect to 10% PL (Fig.…”

Section: Resultsmentioning

confidence: 99%

Platelet Lysate-Derived Neuropeptide y Influences Migration and Angiogenesis of Human Adipose Tissue-Derived Stromal Cells

Businaro

Scaccia

Bordin

et al. 2018

Sci Rep

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Neuropeptide Y (NPY), a powerful neurotransmitter of the central nervous system, is a key regulator of angiogenesis and biology of adipose depots. Intriguingly, its peripheral vascular and angiogenic powerful activity is strictly associated to platelets, which are source of clinical hemoderivates, such as platelet lysate (PL), routinely employed in several clinical applications as wound healing, and to preserve ex vivo the progenitor properties of the adipose stromal cells pool. So far, the presence of NPY in PL and its biological effects on the adipose stromal cell fraction (ASCs) have never been investigated. Here, we aimed to identify endogenous sources of NPY such as PL-based preparations and to investigate which biological properties PL-derived NPY is able to exert on ASCs. The results show that PL contains a high amount of NPY, which is in part also excreted by ASCs when stimulated with PL. The protein levels of the three main NPY subtype receptors (Y1, Y2, Y5) are unaltered by stimulation of ASCs with PL, but their inhibition through selective pharmacological antagonists, considerably enhances migration, and a parallel reduction of angiogenic features of ASCs including decrease in VEGF mRNA and intracellular calcium levels, both downstream targets of NPY. The expression of VEGF and NPY is enhanced within the sites of neovascularisation of difficult wounds in patients after treatment with leuco-platelet concentrates. Our data highlight the presence of NPY in PL preparations and its peripheral effects on adipose progenitors.

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Neuropeptide Y activates phosphorylation of ERK and STAT3 in stromal vascular cells from brown adipose tissue, but fails to affect thermogenic function of brown adipocytes

Cited by 15 publications

References 38 publications

Neuropeptide Y Stimulates Proliferation and Migration of Vascular Smooth Muscle Cells from Pregnancy Hypertensive Rats via Y1 and Y5 Receptors

Neuropeptide Y Stimulates Proliferation and Migration of Vascular Smooth Muscle Cells from Pregnancy Hypertensive Rats via Y1 and Y5 Receptors

Thermogenic Ability of Uncoupling Protein 1 in Beige Adipocytes in Mice

Platelet Lysate-Derived Neuropeptide y Influences Migration and Angiogenesis of Human Adipose Tissue-Derived Stromal Cells

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