LIVIVO - Search results -

Search results

Result 1 - 10 of total 12

Search options

Article ; Online: Development of a hydroxamamide-based bifunctional chelating agent to prepare technetium-99m-labeled bivalent ligand probes

Yoichi Shimizu / Masato Ando / Shimpei Iikuni / Hiroyuki Watanabe / Masahiro Ono

Scientific Reports, Vol 11, Iss 1, Pp 1-

2021 Volume 10

Abstract: Abstract Hydroxamamide (Ham) is a thiol-free chelating agent that forms technetium-99m (99mTc)-complexes with a metal-to-ligand ratio of 1:2 under moderate reaction conditions. Therefore, Ham-based chelating agents will produce 99mTc-labeled compounds ... ...

Abstract	Abstract Hydroxamamide (Ham) is a thiol-free chelating agent that forms technetium-99m (99mTc)-complexes with a metal-to-ligand ratio of 1:2 under moderate reaction conditions. Therefore, Ham-based chelating agents will produce 99mTc-labeled compounds with a bivalent targeting scaffold. For their universal usage, we developed a novel Ham-based bifunctional chelating agent, “Ham-Mal”, with a maleimide group that can easily conjugate with a thiol group, for to preparing 99mTc-labeled bivalent ligand probes. Ham-Mal was synthesized by a four-step reaction, and then reacted with cysteine or c(RGDfC) to produce Ham-Cys or Ham-RGD. These precursors were reacted with 99mTcO4 - for 10 min under room temperature to obtain 99mTc-(Ham-Cys)2 and 99mTc -(Ham-RGD)2. The cellular uptake level of 99mTc-(Ham-RGD)2 by U87MG (high Integrin ɑvβ3 expression) cells was significantly higher than that by PC3 (low Integrin ɑvβ3 expression) cells at 60 min after the incubation, and the uptake was significantly suppressed by pre-treatment for 15 min with excess c(RGDfK) peptide. In the in vivo study with U87MG/PC3 dual xenografted BALB/c-nu mice, the radioactivity of U87MG tumor tissue was significantly higher than that of PC3 tumor tissue at 360 min after the administration of 99mTc-(Ham-RGD)2. These results suggest Ham-Mal may have potential as a bifunctional chelating agent for 99mTc-labeled bivalent ligand probes.
Keywords	Medicine ; R ; Science ; Q
Subject code	500
Language	English
Publishing date	2021-09-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: PET imaging and pharmacological therapy targeting carbonic anhydrase-IX high-expressing tumors using US2 platform based on bivalent ureidosulfonamide.

Shimpei Iikuni / Hiroyuki Watanabe / Yoichi Shimizu / Yuji Nakamoto / Masahiro Ono

PLoS ONE, Vol 15, Iss 12, p e

2020 Volume 0243327

Abstract: Carbonic anhydrase-IX (CA-IX) is attracting much attention as a target molecule for cancer treatment since high expression of CA-IX can lead to a poor prognosis of patients. We previously reported low-molecular-weight 111In/90Y complexes with a bivalent ... ...

Abstract	Carbonic anhydrase-IX (CA-IX) is attracting much attention as a target molecule for cancer treatment since high expression of CA-IX can lead to a poor prognosis of patients. We previously reported low-molecular-weight 111In/90Y complexes with a bivalent ureidosulfonamide scaffold ([111In/90Y]In/Y-US2) as cancer radiotheranostic agents for single photon emission computed tomography and radionuclide-based therapy targeting CA-IX. Here, we applied the US2 platform to positron emission tomography (PET) imaging and pharmacological therapy targeting CA-IX high-expressing tumors by introducing 68Ga and natIn, respectively. In an in vitro cell binding assay, [67Ga]Ga-US2, an alternative complex of [68Ga]Ga-US2 with a longer half-life, markedly bound to CA-IX high-expressing (HT-29) cells compared with low-expressing (MDA-MB-231) cells. In a biodistribution study with HT-29 and MDA-MB-231 tumor-bearing mice, [67Ga]Ga-US2 showed accumulation in the HT-29 tumor (3.81% injected dose/g at 60 min postinjection) and clearance from the blood pool with time. PET with [68Ga]Ga-US2 clearly visualized the HT-29 tumor in model mice at 60 min postinjection. In addition, the administration of [natIn]In-US2 to HT-29 tumor-bearing mice led to tumor growth delay and prolonged mouse survival, while no critical toxicity was observed. These results indicate that [68Ga]Ga-US2 and [natIn]In-US2 may be useful imaging and therapeutic agents targeting CA-IX, respectively, and that US2 may serve as an effective cancer theranostic platform utilizing CA-IX.
Keywords	Medicine ; R ; Science ; Q
Subject code	616
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Nursing support for breathlessness in patients with cancer

Jun Kako / Kohei Kajiwara / Masamitsu Kobayashi / Yoichi Shimizu / Taichi Shimazu / Yoshinobu Matsuda / Megumi Hori / Miho Suzuki / Yusuke Kanno / Kimiko Nakano / Miharu Morikawa / Mariko Niino

BMJ Open, Vol 13, Iss

a scoping review

2023 Volume 10

Abstract: Objective To identify nursing support provided for the relief of breathlessness in patients with cancer.Design A scoping review following a standard framework proposed by Arksey and O’Malley.Study selection Electronic databases (PubMed, CINAHL, CENTRAL ... ...

Abstract	Objective To identify nursing support provided for the relief of breathlessness in patients with cancer.Design A scoping review following a standard framework proposed by Arksey and O’Malley.Study selection Electronic databases (PubMed, CINAHL, CENTRAL and Ichushi-Web of the Japan Medical Abstract Society Databases) were searched from inception to 31 January 2022. Studies reporting on patients with cancer (aged ≥18 years), intervention for relief from breathlessness, nursing support and quantitatively assessed breathlessness using a scale were included.Results Overall, 2629 articles were screened, and 27 were finally included. Results of the qualitative thematic analysis were categorised into 12 nursing support components: fan therapy, nurse-led intervention, multidisciplinary intervention, psychoeducational programme, breathing technique, walking therapy, inspiratory muscle training, respiratory rehabilitation, yoga, acupuncture, guided imagery and abdominal massage.Conclusions We identified 12 components of nursing support for breathlessness in patients with cancer. The study results may be useful to understand the actual state of nursing support provided for breathlessness in patients with terminal cancer and to consider possible support that can be implemented.
Keywords	Medicine ; R
Subject code	610
Language	English
Publishing date	2023-10-01T00:00:00Z
Publisher	BMJ Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Increased [18F]FMISO accumulation under hypoxia by multidrug-resistant protein 1 inhibitors

Yoichi Shimizu / Yukihiro Nakai / Hiroyuki Watanabe / Shimpei Iikuni / Masahiro Ono / Hideo Saji / Yuji Kuge / Tsuneo Saga / Yuji Nakamoto

EJNMMI Research, Vol 11, Iss 1, Pp 1-

2021 Volume 6

Abstract: Abstract Background [18F]Fluoromisonidazole ([18F]FMISO) is a PET imaging probe widely used for the detection of hypoxia. We previously reported that [18F]FMISO is metabolized to the glutathione conjugate of the reduced form in hypoxic cells. In addition, ...

Abstract	Abstract Background [18F]Fluoromisonidazole ([18F]FMISO) is a PET imaging probe widely used for the detection of hypoxia. We previously reported that [18F]FMISO is metabolized to the glutathione conjugate of the reduced form in hypoxic cells. In addition, we found that the [18F]FMISO uptake level varied depending on the cellular glutathione conjugation and excretion ability such as enzyme activity of glutathione-S-transferase and expression levels of multidrug resistance-associated protein 1 (MRP1, an efflux transporter), in addition to the cellular hypoxic state. In this study, we evaluated whether MRP1 activity affected [18F]FMISO PET imaging. Methods FaDu human pharyngeal squamous cell carcinoma cells were pretreated with MRP1 inhibitors (cyclosporine A, lapatinib, or MK-571) for 1 h, incubated with [18F]FMISO for 4 h under hypoxia, and their radioactivity was then measured. FaDu tumor-bearing mice were intravenously injected with [18F]FMISO, and PET/CT images were acquired at 4 h post-injection (1st PET scan). Two days later, the same mice were pretreated with MRP1 inhibitors (cyclosporine A, lapatinib, or MK-571) for 1 h, and PET/CT images were acquired (2nd PET scan). Results FaDu cells pretreated with MRP1 inhibitors exhibited significantly higher radioactivity than those without inhibitor treatment (cyclosporine A: 6.91 ± 0.27, lapatinib: 10.03 ± 0.47, MK-571: 10.15 ± 0.44%dose/mg protein, p < 0.01). In the in vivo PET study, the SUVmean ratio in tumors [calculated as after treatment (2nd PET scan)/before treatment of MRP1 inhibitors (1st PET scan)] of the mice treated with MRP1 inhibitors was significantly higher than those of control mice (cyclosporine A: 2.6 ± 0.7, lapatinib: 2.2 ± 0.7, MK-571: 2.2 ± 0.7, control: 1.2 ± 0.2, p < 0.05). Conclusion In this study, we revealed that MRP1 inhibitors increase [18F]FMISO accumulation in hypoxic cells. This suggests that [18F]FMISO-PET imaging is affected by MRP1 inhibitors independent of the hypoxic state.
Keywords	[18F]FMISO ; Hypoxia ; MRP1 ; Medical physics. Medical radiology. Nuclear medicine ; R895-920
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	SpringerOpen
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Development of Technetium-99m-Labeled BODIPY-Based Probes Targeting Lipid Droplets Toward the Diagnosis of Hyperlipidemia-Related Diseases

Yoichi Shimizu / Keiichi Tanimura / Shimpei Iikuni / Hiroyuki Watanabe / Hideo Saji / Masahiro Ono

Molecules, Vol 24, Iss 12, p

2019 Volume 2283

Abstract: Hyperlipidemia causes systemic lipid disorder, which leads to hepatic steatosis and atherosclerosis. Thus, it is necessary to detect these syndromes early and precisely to improve prognosis. In the affected regions, abnormal formation and growth of lipid ...

Abstract	Hyperlipidemia causes systemic lipid disorder, which leads to hepatic steatosis and atherosclerosis. Thus, it is necessary to detect these syndromes early and precisely to improve prognosis. In the affected regions, abnormal formation and growth of lipid droplets is observed; therefore, lipid droplets may be a suitable target for the diagnosis of hyperlipidemia-related syndromes. In this study, we designed and synthesized [ 99m Tc]Tc-BOD and [ 99m Tc]Tc-MBOD composed of one technetium-99m and two BODIPY scaffolds with hydroxamamide (Ham) or N -methylated hydroxamamide (MHam) in radiochemical yields of 54 and 35%, respectively, with a radiochemical purity of over 95%. [ 99m Tc]Tc-BOD showed significantly higher accumulation levels in foam cells than in non-foam cells (foam cells: 213.8 ± 64.8, non-foam cell: 126.2 ± 26.9 %dose/mg protein, p < 0.05) 2 h after incubation. In contrast, [ 99m Tc]Tc-MBOD showed similar accumulation levels in foam cells and non-foam cells (foam cells: 92.2 ± 23.3, non-foam cell: 83.8 ± 19.8 %dose/mg protein). In normal mice, [ 99m Tc]Tc-BOD exhibited gradual blood clearance (0.5 h: 4.98 ± 0.35, 6 h: 1.94 ± 0.12 %ID/g) and relatively high accumulation in the liver 6 h after administration (15.22 ± 1.72 %ID/g). Therefore, [ 99m Tc]Tc-BOD may have potential as an imaging probe for detecting lipid droplets in disease lesions of hyperlipidemia.
Keywords	technetium-99m ; hyperlipidemia ; hydroxamamide ; BODIPY ; Organic chemistry ; QD241-441
Language	English
Publishing date	2019-06-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Distinctive detection of insulinoma using [18F]FB(ePEG12)12-exendin-4 PET/CT

Takaaki Murakami / Hiroyuki Fujimoto / Keita Hamamatsu / Yuki Yamauchi / Yuzo Kodama / Naotaka Fujita / Junji Fujikura / Yoichi Shimizu / Yuji Nakamoto / Hiroyuki Kimura / Hideo Saji / Nobuya Inagaki

Scientific Reports, Vol 11, Iss 1, Pp 1-

2021 Volume 12

Abstract: Abstract Specifying the exact localization of insulinoma remains challenging due to the lack of insulinoma-specific imaging methods. Recently, glucagon-like peptide-1 receptor (GLP-1R)-targeted imaging, especially positron emission tomography (PET), has ... ...

Abstract	Abstract Specifying the exact localization of insulinoma remains challenging due to the lack of insulinoma-specific imaging methods. Recently, glucagon-like peptide-1 receptor (GLP-1R)-targeted imaging, especially positron emission tomography (PET), has emerged. Although various radiolabeled GLP-1R agonist exendin-4-based probes with chemical modifications for PET imaging have been investigated, an optimal candidate probe and its scanning protocol remain a necessity. Thus, we investigated the utility of a novel exendin-4-based probe conjugated with polyethylene glycol (PEG) for [18F]FB(ePEG12)12-exendin-4 PET imaging for insulinoma detection. We utilized [18F]FB(ePEG12)12-exendin-4 PET/CT to visualize mouse tumor models, which were generated using rat insulinoma cell xenografts. The probe demonstrated high uptake value on the tumor as 37.1 ± 0.4%ID/g, with rapid kidney clearance. Additionally, we used Pdx1-Cre;Trp53 R172H ;Rb f/f mice, which developed endogenous insulinoma and glucagonoma, since they enabled differential imaging evaluation of our probe in functional pancreatic neuroendocrine neoplasms. In this model, our [18F]FB(ePEG12)12-exendin-4 PET/CT yielded favorable sensitivity and specificity for insulinoma detection. Sensitivity: 30-min post-injection 66.7%, 60-min post-injection 83.3%, combined 100% and specificity: 30-min post-injection 100%, 60-min post-injection 100%, combined 100%, which was corroborated by the results of in vitro time-based analysis of internalized probe accumulation. Accordingly, [18F]FB(ePEG12)12-exendin-4 is a promising PET imaging probe for visualizing insulinoma.
Keywords	Medicine ; R ; Science ; Q
Subject code	500
Language	English
Publishing date	2021-07-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Elimination of tumor hypoxia by eribulin demonstrated by 18F-FMISO hypoxia imaging in human tumor xenograft models

Songji Zhao / Wenwen Yu / Naoyuki Ukon / Chengbo Tan / Ken-ichi Nishijima / Yoichi Shimizu / Kei Higashikawa / Tohru Shiga / Hiroko Yamashita / Nagara Tamaki / Yuji Kuge

EJNMMI Research, Vol 9, Iss 1, Pp 1-

2019 Volume 10

Abstract: Abstract Background Eribulin, an inhibitor of microtubule dynamics, shows antitumor potency against a variety of solid cancers through its antivascular activity and remodeling of tumor vasculature. 18F-Fluoromisonidazole (18F-FMISO) is the most widely ... ...

Abstract	Abstract Background Eribulin, an inhibitor of microtubule dynamics, shows antitumor potency against a variety of solid cancers through its antivascular activity and remodeling of tumor vasculature. 18F-Fluoromisonidazole (18F-FMISO) is the most widely used PET probe for imaging tumor hypoxia. In this study, we utilized 18F-FMISO to clarify the effects of eribulin on the tumor hypoxic condition in comparison with histological findings. Material and methods Mice bearing a human cancer cell xenograft were intraperitoneally administered a single dose of eribulin (0.3 or 1.0 mg/kg) or saline. Three days after the treatment, mice were injected with 18F-FMISO and pimonidazole (hypoxia marker for immunohistochemistry), and intertumoral 18F-FMISO accumulation levels and histological characteristics were determined. PET/CT was performed pre- and post-treatment with eribulin (0.3 mg/kg, i.p.). Results The 18F-FMISO accumulation levels and percent pimonidazole-positive hypoxic area were significantly lower, whereas the number of microvessels was higher in the tumors treated with eribulin. The PET/CT confirmed that 18F-FMISO distribution in the tumor was decreased after the eribulin treatment. Conclusions Using 18F-FMISO, we demonstrated the elimination of the tumor hypoxic condition by eribulin treatment, concomitantly with the increase in microvessel density. These findings indicate that PET imaging using 18F-FMISO may provide the possibility to detect the early treatment response in clinical patients undergoing eribulin treatment.
Keywords	Eribulin ; Tumor hypoxia ; 18F-FMISO PET imaging ; Remodeling of tumor vasculature ; Human tumor xenograft model ; Medical physics. Medical radiology. Nuclear medicine ; R895-920
Subject code	610
Language	English
Publishing date	2019-06-01T00:00:00Z
Publisher	SpringerOpen
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Imaging Mass Spectrometry Revealed the Accumulation Characteristics of the 2-Nitroimidazole-Based Agent "Pimonidazole" in Hypoxia.

Yukiko Masaki / Yoichi Shimizu / Takeshi Yoshioka / Fei Feng / Songji Zhao / Kenichi Higashino / Yoshito Numata / Yuji Kuge

PLoS ONE, Vol 11, Iss 8, p e

2016 Volume 0161639

Abstract: Hypoxia, or low oxygen concentration, is a key factor promoting tumor progression and angiogenesis and resistance of cancer to radiotherapy and chemotherapy. 2-Nitroimidazole-based agents have been widely used in pathological and nuclear medicine ... ...

Abstract	Hypoxia, or low oxygen concentration, is a key factor promoting tumor progression and angiogenesis and resistance of cancer to radiotherapy and chemotherapy. 2-Nitroimidazole-based agents have been widely used in pathological and nuclear medicine examinations to detect hypoxic regions in tumors; in particular, pimonidazole is used for histochemical staining of hypoxic regions. It is considered to accumulate in hypoxic cells via covalent binding with macromolecules or by forming reductive metabolites after reduction of its nitro group. However, the detailed mechanism of its accumulation remains unknown. In this study, we investigated the accumulation mechanism of pimonidazole in hypoxic tumor tissues in a mouse model by mass spectrometric analyses including imaging mass spectrometry (IMS). Pimonidazole and its reductive metabolites were observed in the tumor tissues. However, their locations in the tumor sections were not similar to the positively stained areas in pimonidazole-immunohistochemistry, an area considered hypoxic. The glutathione conjugate of reduced pimonidazole, a low-molecular-weight metabolite of pimonidazole, was found in tumor tissues by LC-MS analysis, and our IMS study determined that the intratumor localization of the glutathione conjugate was consistent with the area positively immunostained for pimonidazole. We also found complementary localization of the glutathione conjugate and reduced glutathione (GSH), implying that formation of the glutathione conjugate occurred in the tumor tissue. These results suggest that in hypoxic tumor cells, pimonidazole is reduced at its nitro group, followed by conjugation with GSH.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2016-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Imaging Mass Spectrometry Reveals Acyl-Chain- and Region-Specific Sphingolipid Metabolism in the Kidneys of Sphingomyelin Synthase 2-Deficient Mice.

Masayuki Sugimoto / Masato Wakabayashi / Yoichi Shimizu / Takeshi Yoshioka / Kenichi Higashino / Yoshito Numata / Tomohiko Okuda / Songji Zhao / Shota Sakai / Yasuyuki Igarashi / Yuji Kuge

PLoS ONE, Vol 11, Iss 3, p e

2016 Volume 0152191

Abstract: Obesity was reported to cause kidney injury by excessive accumulation of sphingolipids such as sphingomyelin and ceramide. Sphingomyelin synthase 2 (SMS2) is an important enzyme for hepatic sphingolipid homeostasis and its dysfunction is considered to ... ...

Abstract	Obesity was reported to cause kidney injury by excessive accumulation of sphingolipids such as sphingomyelin and ceramide. Sphingomyelin synthase 2 (SMS2) is an important enzyme for hepatic sphingolipid homeostasis and its dysfunction is considered to result in fatty liver disease. The expression of SMS2 is also high in the kidneys. However, the contribution of SMS2 on renal sphingolipid metabolism remains unclear. Imaging mass spectrometry is a powerful tool to visualize the distribution and provide quantitative data on lipids in tissue sections. Thus, in this study, we analyzed the effects of SMS2 deficiency on the distribution and concentration of sphingomyelins in the liver and kidneys of mice fed with a normal-diet or a high-fat-diet using imaging mass spectrometry and liquid chromatography/electrospray ionization-tandem mass spectrometry. Our study revealed that high-fat-diet increased C18-C22 sphingomyelins, but decreased C24-sphingomyelins, in the liver and kidneys of wild-type mice. By contrast, SMS2 deficiency decreased C18-C24 sphingomyelins in the liver. Although a similar trend was observed in the whole-kidneys, the effects were minor. Interestingly, imaging mass spectrometry revealed that sphingomyelin localization was specific to each acyl-chain length in the kidneys. Further, SMS2 deficiency mainly decreased C22-sphingomyelin in the renal medulla and C24-sphingomyelins in the renal cortex. Thus, imaging mass spectrometry can provide visual assessment of the contribution of SMS2 on acyl-chain- and region-specific sphingomyelin metabolism in the kidneys.
Keywords	Medicine ; R ; Science ; Q
Subject code	616
Language	English
Publishing date	2016-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article: Histological analyses by matrix-assisted laser desorption/ionization-imaging mass spectrometry reveal differential localization of sphingomyelin molecular species regulated by particular ceramide synthase in mouse brains

Sugimoto, Masayuki / Akio Kihara / Kenichi Higashino / Masato Wakabayashi / Shota Sakai / Takeshi Yoshioka / Yasuyuki Igarashi / Yoichi Shimizu / Yoshito Numata / Yuji Kuge / Yukari Tanaka

Biochimica et biophysica acta. 2015 Dec., v. 1851, no. 12

2015

Abstract: Sphingomyelin (SM) is synthesized by SM synthase (SMS) from ceramide (Cer). SM regulates signaling pathways and maintains organ structure. SM comprises a sphingoid base and differing lengths of acyl-chains, but the importance of its various forms and ... ...

Abstract	Sphingomyelin (SM) is synthesized by SM synthase (SMS) from ceramide (Cer). SM regulates signaling pathways and maintains organ structure. SM comprises a sphingoid base and differing lengths of acyl-chains, but the importance of its various forms and regulatory synthases is not known. It has been reported that Cer synthase (CerS) has restricted substrate specificity, whereas SMS has no specificity for different lengths of acyl-chains. We hypothesized that the distribution of each SM molecular species was regulated by expression of the CerS family. Thus, we compared the distribution of SM species and CerS mRNA expression using molecular imaging. Spatial distribution of each SM molecular species was investigated using ultra-high-resolution imaging mass spectrometry (IMS). IMS revealed that distribution of SM molecular species varied according to the lengths of acyl-chains found in each brain section. Furthermore, a combination study using in situ hybridization and IMS revealed the spatial expression of CerS1 to be associated with the localization of SM (d18:1/18:0) in cell body-rich gray matter, and CerS2 to be associated with SM (d18:1/24:1) in myelin-rich white matter. Our study is the first comparison of spatial distribution between SM molecular species and CerS isoforms, and revealed their distinct association in the brain. These observations were demonstrated by suppression of CerS2 using siRNA in HepG2 cells; that is, siRNA for CerS2 specifically decreased C22 very long-chain fatty acid (VLCFA)- and C24 VLCFA-containing SMs. Thus, histological analyses of SM species by IMS could be a useful approach to consider their molecular function and regulative mechanism.
Keywords	brain ; ceramides ; gene expression ; human cell lines ; image analysis ; in situ hybridization ; mass spectrometry ; messenger RNA ; mice ; signal transduction ; small interfering RNA ; sphingomyelins ; sphingosine N-acyltransferase ; substrate specificity ; very long chain fatty acids
Language	English
Dates of publication	2015-12
Size	p. 1554-1565.
Publishing place	Elsevier B.V.
Document type	Article
ISSN	1388-1981
DOI	10.1016/j.bbalip.2015.09.004
Database	NAL-Catalogue (AGRICOLA)

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

To top

Full text online

More links

Kategorien

Inter-library loan at ZB MED

Full text online

More links

Kategorien

Inter-library loan at ZB MED

Full text online

More links

Kategorien

Inter-library loan at ZB MED

Full text online

More links

Kategorien

Inter-library loan at ZB MED

Full text online

More links

Kategorien

Inter-library loan at ZB MED

Full text online

More links

Kategorien

Inter-library loan at ZB MED

Full text online

More links

Kategorien

Inter-library loan at ZB MED

Full text online

More links

Kategorien

Inter-library loan at ZB MED

Full text online

More links

Kategorien

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

Inter-library loan at ZB MED