Effects of progesterone on glucose uptake in neurons of Alzheimer's disease animals and cell models

Wu, Hang; Wu, Zhigang; Shi, Wenjing; Gao, Hui; Wu, Honghai; Bian, Fang; Jia, Pengpeng; Yan-ning, Hou

doi:10.1016/j.lfs.2019.116979

Cited by 30 publications

(22 citation statements)

References 61 publications

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“…Sabbir [25] recently reported that PGRMC1 induced a P4-dependent metabolic change resembling the Warburg effect in HEK293 cells, which was associated with changes in PGRMC1 stability, posttranslational modifications, and subcellular locations. PGRMC1 regulation of glucose metabolism is supported by its implicated mediation of the placental P4dependent shift from aerobic towards anaerobic glucose metabolism in gestational diabetes [26], association with the insulin receptor and glucose transporters [27], and probable involvement (based upon AG-205 sensitivity) in P4-mediated increase in neuronal glycolysis [28].…”

Section: Introductionmentioning

confidence: 99%

PGRMC1 phosphorylation affects cell shape, motility, glycolysis, mitochondrial form and function, and tumor growth

Thejer

Adhikary

Kaur

et al. 2020

BMC Mol and Cell Biol

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Background Progesterone Receptor Membrane Component 1 (PGRMC1) is expressed in many cancer cells, where it is associated with detrimental patient outcomes. It contains phosphorylated tyrosines which evolutionarily preceded deuterostome gastrulation and tissue differentiation mechanisms. Results We demonstrate that manipulating PGRMC1 phosphorylation status in MIA PaCa-2 (MP) cells imposes broad pleiotropic effects. Relative to parental cells over-expressing hemagglutinin-tagged wild-type (WT) PGRMC1-HA, cells expressing a PGRMC1-HA-S57A/S181A double mutant (DM) exhibited reduced levels of proteins involved in energy metabolism and mitochondrial function, and altered glucose metabolism suggesting modulation of the Warburg effect. This was associated with increased PI3K/AKT activity, altered cell shape, actin cytoskeleton, motility, and mitochondrial properties. An S57A/Y180F/S181A triple mutant (TM) indicated the involvement of Y180 in PI3K/AKT activation. Mutation of Y180F strongly attenuated subcutaneous xenograft tumor growth in NOD-SCID gamma mice. Elsewhere we demonstrate altered metabolism, mutation incidence, and epigenetic status in these cells. Conclusions Altogether, these results indicate that mutational manipulation of PGRMC1 phosphorylation status exerts broad pleiotropic effects relevant to cancer and other cell biology.

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Section: Introductionmentioning

confidence: 99%

PGRMC1 phosphorylation affects cell shape, motility, glycolysis, mitochondrial form and function, and tumor growth

Thejer

Adhikary

Kaur

et al. 2020

BMC Mol and Cell Biol

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“…For detailed investigation of AD formation, various in vivo and in vitro experiments have been performed (Wu et al, 2019) in order to follow the molecular biological alterations. There are a few genetically modified mice with tau and Aβ overexpression showing macroscopical and molecular biological disorders of AD (Radak et al, 2010;Abraham et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Physical Activity Protects the Pathological Alterations of Alzheimer’s Disease Kidneys via the Activation of PACAP and BMP Signaling Pathways

Perényi

Szegeczki

Horváth

et al. 2020

Front. Cell. Neurosci.

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Alzheimer's disease (AD) is a neurodegenerative disorder with typical amyloid beta (Aβ) aggregations. Elimination of the Aβ precursors via the kidneys makes the organ a potential factor in the systemic degeneration leading to AD. Pituitary adenylate cyclase-activating polypeptide (PACAP) exerts neuroprotective effects in AD and plays a protective role in kidney pathologies. Increased physical activity is preventive of the formation of AD, but its detailed mechanism and possible connections with PACAP have not been clarified. In the kidneys of AD mice, the effects of physical activity were investigated by comparing wild-type and AD organs. Aβ plaque formation was reduced in AD kidneys after increased training (TAD). Mechanotransduction elevated PACAP receptor expression in TAD mice and normalized the protein kinase A (PKA)-mediated pathways. BMP4/BMPR1 elevation activated Smad1 expression and normalized collagen type IV in TAD animals. In conclusion, our data suggest that elevated physical activity can prevent the AD-induced pathological changes in the kidneys via, at least in part, the activation of PACAP-BMP signaling crosstalk.

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“…However, we have shown previously that necrosis, autophagy, apoptosis, and ferroptosis are involved in neuronal death in the acute period after ICH 31 , 43 . Therefore, even though investigators have reported that higher neuronal GLUT3 benefits neuronal function and learning in Alzheimer’s disease 44 – 46 , it seems less likely in our study. Neuronal death in the ipsilateral striatum certainly contributed to the glucose hypometabolism detected in 18 F-FDG-PET imaging.…”

Section: Discussionmentioning

confidence: 58%

Analysis of glucose metabolism by 18F-FDG-PET imaging and glucose transporter expression in a mouse model of intracerebral hemorrhage

Han

Ren

Nandi

et al. 2021

Sci Rep

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The relationship between cerebral glucose metabolism and glucose transporter expression after intracerebral hemorrhage (ICH) is unclear. Few studies have used positron emission tomography (PET) to explore cerebral glucose metabolism after ICH in rodents. In this study, we produced ICH in mice with an intrastriatal injection of collagenase to investigate whether glucose metabolic changes in 18F-fluoro-2-deoxy-D-glucose (FDG)-PET images are associated with expression of glucose transporters (GLUTs) over time. On days 1 and 3 after ICH, the ipsilateral striatum exhibited significant hypometabolism. However, by days 7 and 14, glucose metabolism was significantly higher in the ipsilateral striatum than in the contralateral striatum. The contralateral hemisphere did not show hypermetabolism at any time after ICH. Qualitative immunofluorescence and Western blotting indicated that the expression of GLUT1 in ipsilateral striatum decreased on days 1 and 3 after ICH and gradually returned to baseline by day 21. The 18F-FDG uptake after ICH was associated with expression of GLUT1 but not GLUT3 or GLUT5. Our data suggest that ipsilateral cerebral glucose metabolism decreases in the early stage after ICH and increases progressively in the late stage. Changes in 18F-FDG uptake on PET imaging are associated with the expression of GLUT1 in the ipsilateral striatum.

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Effects of progesterone on glucose uptake in neurons of Alzheimer's disease animals and cell models

Cited by 30 publications

References 61 publications

PGRMC1 phosphorylation affects cell shape, motility, glycolysis, mitochondrial form and function, and tumor growth

PGRMC1 phosphorylation affects cell shape, motility, glycolysis, mitochondrial form and function, and tumor growth

Physical Activity Protects the Pathological Alterations of Alzheimer’s Disease Kidneys via the Activation of PACAP and BMP Signaling Pathways

Analysis of glucose metabolism by 18F-FDG-PET imaging and glucose transporter expression in a mouse model of intracerebral hemorrhage

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