Steryl Glucoside is a Lipid Mediator in Stress-responsive Signal Transduction.

Kunimoto, Shohko; Murofushi, Wataru; Kai, Hirofumi; Ishida, Yasushi; Uchiyama, Ayako; Kobayashi, Tetsuyuki; Kobayashi, Susumu; Murofushi, Hiromu; Murakami‐Murofushi, Kimiko

doi:10.1247/csf.27.157

Cited by 65 publications

(52 citation statements)

References 32 publications

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“…The synthesis of such molecules presumably depends on enzymes similar in function to sterol glucosyltransferase (Warnecke et al 1997). Evidence that such synthesis of sterol glucosides can occur in human cells has been demonstrated for human fibroblasts in culture following heat shock (Kunimoto et al 2000(Kunimoto et al , 2002 and recently in our laboratory by serum derprivation (Ly et al in preparation). A third source may involve infectious agents.…”

Section: Discussionmentioning

confidence: 85%

“…In contrast, cholesterol glucoside has been implicated as playing a primary role in the early stages of stress-induced signal transduction in various animal cells, including cultured human fibroblasts (Murakami-Murofushi et al 1997;Kunimoto et al 2000Kunimoto et al , 2002. The cumulative data thus clearly demonstrate that sterol glucosides from plants or animal cells are not uniform in their actions and may span the range of actions from protective to toxic.…”

Section: Introductionmentioning

confidence: 96%

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Chronic Exposure to Dietary Sterol Glucosides is Neurotoxic to Motor Neurons and Induces an ALS–PDC Phenotype

Tabata

Wilson

et al. 2008

Neuromol Med

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Epidemiological studies of the Guamanian variants of amyotrophic lateral sclerosis (ALS) and parkinsonism, amyotrophic lateral sclerosis-parkinsonism dementia complex (ALS-PDC), have shown a positive correlation between consumption of washed cycad seed flour and disease occurrence. Previous in vivo studies by our group have shown that the same seed flour induces ALS and PDC phenotypes in out bred adult male mice. In vitro studies using isolated cycad compounds have also demonstrated that several of these are neurotoxic, specifically, a number of water insoluble phytosterol glucosides of which β-sitosterol β-D-glucoside (BSSG) forms the largest fraction. BSSG is neurotoxic to motor neurons and other neuronal populations in culture. The present study shows that an in vitro hybrid motor neuron (NSC-34) culture treated with BSSG undergoes a dose-dependent cell loss. Surviving cells show increased expression of HSP70, decreased cytosolic heavy neurofilament expression, and have various morphological abnormalities. CD-1 mice fed mouse NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript chow pellets containing BSSG for 15 weeks showed motor deficits and motor neuron loss in the lumbar and thoracic spinal cord, along with decreased glutamate transporter labelling, and increased glial fibrillary acid protein reactivity. Other pathological outcomes included increased caspase-3 labelling in the striatum and decreased tyrosine-hydroxylase labelling in the striatum and substantia nigra. C57BL/6 mice fed BSSG-treated pellets for 10 weeks exhibited progressive loss of motor neurons in the lumbar spinal cord that continued to worsen even after the BSSG exposure ended. These results provide further support implicating sterol glucosides as one potential causal factor in the motor neuron pathology previously associated with cycad consumption and ALS-PDC.

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Section: Discussionmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 96%

Chronic Exposure to Dietary Sterol Glucosides is Neurotoxic to Motor Neurons and Induces an ALS–PDC Phenotype

Tabata

Wilson

et al. 2008

Neuromol Med

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“…How cholesterol homeostasis is regulated during heat or BA stress and also during the subsequent adaptation phase is currently under investigation in our laboratory. The increased susceptibility (chemical potential) of cholesterol displaced from plasma membrane lipids may also be linked to the formation of cholesterol glucoside, a known lipid mediator that rapidly activates HSF1 and induces the formation of Hsp70 (32).…”

Section: Discussionmentioning

confidence: 99%

Hyperfluidization-coupled membrane microdomain reorganization is linked to activation of the heat shock response in a murine melanoma cell line

Nagy

Balogi

Gombos

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

104

126

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Targeting of the Hsp function in tumor cells is currently being assessed as potential anticancer therapy. An improved understanding of the molecular signals that trigger or attenuate the stress protein response is essential for advances to be made in this field. The present study provides evidence that the membrane fluidizer benzyl alcohol (BA), a documented nondenaturant, acts as a chaperone inducer in B16(F10) melanoma cells. It is demonstrated that this effect relies basically on heat shock transcription factor 1 (HSF1) activation. Under the conditions tested, the BA-induced Hsp response involves the up-regulation of a subset of hsp genes. It is shown that the same level of membrane fluidization (estimated in the core membrane region) attained with the closely analogous phenethyl alcohol (PhA) does not generate a stress protein signal. BA, at a concentration that activates heat shock genes, exerts a profound effect on the melting of raft-like cholesterolsphingomyelin domains in vitro, whereas PhA, at a concentration equipotent with BA in membrane fluidization, has no such effect. Furthermore, through the in vivo labeling of melanoma cells with a fluorescein labeled probe that inserts into the cholesterol-rich membrane domains [fluorescein ester of polyethylene glycol-derivatized cholesterol (fPEG-Chol)], we found that, similarly to heat stress per se, BA, but not PhA, initiates profound alterations in the plasma membrane microdomain structure. We suggest that, apart from membrane hyperfluidization in the deep hydrophobic region, a distinct reorganization of cholesterol-rich microdomains may also be required for the generation and transmission of stress signals to activate hsp genes. molecular chaperones ͉ stress signaling ͉ membrane defects ͉ rafts ͉ cancer therapy

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“…Diacylglycerol is glycosylated to form galactosyldiacylglycerol. Most recent studies show that cholesterol can also be modified with glucose (36). These glycosylated lipids play significant roles in a variety of biological processes, including cellular proliferation, development, differentiation, and stress responses (35,37).…”

Section: Discussionmentioning

confidence: 99%

Carbohydrate-dependent signaling from the phosphatidylglucoside-based microdomain induces granulocytic differentiation of HL60 cells

Nagatsuka

Miki

Kasama

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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Steryl Glucoside is a Lipid Mediator in Stress-responsive Signal Transduction.

Cited by 65 publications

References 32 publications

Chronic Exposure to Dietary Sterol Glucosides is Neurotoxic to Motor Neurons and Induces an ALS–PDC Phenotype

Chronic Exposure to Dietary Sterol Glucosides is Neurotoxic to Motor Neurons and Induces an ALS–PDC Phenotype

Hyperfluidization-coupled membrane microdomain reorganization is linked to activation of the heat shock response in a murine melanoma cell line

Carbohydrate-dependent signaling from the phosphatidylglucoside-based microdomain induces granulocytic differentiation of HL60 cells

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