Changes in Lipid Composition During Manganese-Induced Apoptosis in PC12 Cells

Corsetto, P.A.; Ferrara, Giuseppina; Buratta, Sandra; Urbanelli, Lorena; Montorfano, G.; Gambelunghe, Angela; Chiaradia, Elisabetta; Magini, Alessandro; Roderi, P.; Colombo, Irma; Rizzo, Angela Maria; Emiliani, Carla

doi:10.1007/s11064-015-1785-9

Cited by 9 publications

(4 citation statements)

References 55 publications

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“…1B). There was no significant cytotoxicity observed in treated cells, which is consistent with other reports (11,62). We therefore chose the intermediate concentration of 0.2 mM MnCl 2 for all experiments.…”

Section: Mncl 2 Causes Intracellular Accumulation Of Aqp2 In Cultured Cells and Kidney Slicessupporting

confidence: 88%

Manganese promotes intracellular accumulation of AQP2 via modulating F-actin polymerization and reduces urinary concentration in mice

Lei

Huang

et al. 2018

American Journal of Physiology-Renal Physiology

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Aquaporin-2 (AQP2) is a water channel protein expressed in principal cells (PCs) of the kidney collecting ducts (CDs) and plays a critical role in mediating water reabsorption and urine concentration. AQP2 undergoes both regulated trafficking mediated by vasopressin (VP) and constitutive recycling, which is independent of VP. For both pathways, actin cytoskeletal dynamics is a key determinant of AQP2 trafficking. We report here that manganese chloride (MnCl) is a novel and potent regulator of AQP2 trafficking in cultured cells and in the kidney. MnCl treatment promoted internalization and intracellular accumulation of AQP2. The effect of MnCl on the intracellular accumulation of AQP2 was associated with activation of RhoA and actin polymerization without modification of AQP2 phosphorylation. Although the level of total and phosphorylated AQP2 did not change, MnCl treatment impeded VP-induced phosphorylation of AQP2 at its serine-256, -264, and -269 residues and dephosphorylation at serine 261. In addition, MnCl significantly promoted F-actin polymerization along with downregulation of RhoA activity and prevented VP-induced membrane accumulation of AQP2. Finally, MnCl treatment in mice resulted in significant polyuria and reduced urinary concentration, likely due to intracellular relocation of AQP2 in the PCs of kidney CDs. More importantly, the reduced urinary concentration caused by MnCl treatment in animals was not corrected by VP. In summary, our study identified a novel effect of MnCl on AQP2 trafficking through modifying RhoA activity and actin polymerization and uncovered its potent impact on water diuresis in vivo.

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Section: Mncl 2 Causes Intracellular Accumulation Of Aqp2 In Cultured Cells and Kidney Slicessupporting

confidence: 88%

Manganese promotes intracellular accumulation of AQP2 via modulating F-actin polymerization and reduces urinary concentration in mice

Lei

Huang

et al. 2018

American Journal of Physiology-Renal Physiology

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“…The PL and neutral lipid (NL) quantifications were achieved as previously described by high-pressure liquid chromatography (HPLC) (Jasco, Tokyo, Japan) equipped with an ELSD detector (Sedere, Alfortville Cedex, Paris, France) and silica normal-phase LiChrospher Si 60 column (LiChroCART 250-4; Merck, Darmstadt, Germany) [16].…”

Section: Lipid Extraction and Analysismentioning

confidence: 99%

Exogenous Fatty Acids Modulate ER Lipid Composition and Metabolism in Breast Cancer Cells

Rizzo¹,

Colombo²,

Montorfano³

et al. 2021

Cells

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(1) Background: Lipid metabolism is a fundamental hallmark of all tumors, especially of breast cancer. Few studies describe the different lipid metabolisms and sensitivities to the microenvironment of breast cancer cell subtypes that influence the proliferation, aggressiveness, and success of therapy. This study describes the impact of lipid microenvironment on endoplasmic reticulum (ER) membrane and metabolic activity in two breast cancer cell lines with Luminal A and triple-negative breast cancer (TNBC) features. (2) Methods: We investigated the peculiar lipid phenotype of a TNBC cell line, MDA-MB-231, and a Luminal A cell line, MCF7, and their different sensitivity to exogenous fatty acids (i.e., palmitic acid (PA) and docosahexaenoic acid (DHA)). Moreover, we verified the impact of exogenous fatty acids on ER lipid composition. (3) Results: The data obtained demonstrate that MDA-MB-231 cells are more sensitive to the lipid microenvironment and that both PA and DHA are able to remodel their ER membranes with consequences on resident enzyme activity. On the contrary, MCF7 cells are less sensitive to PA, whereas they incorporate DHA, although less efficiently than MDA-MB-231 cells. (4) Conclusions: This study sustains the importance of lipid metabolism as an innovative hallmark to discriminate breast cancer subclasses and to develop personalized and innovative pharmacological strategies. The different sensitivities to the lipid environment shown by MCF7 and MDA-MB-231 cells might be related to cell malignancy and chemoresistance onset. In the future, this new approach could lead to a substantial decrease both in deleterious side effects for the patients and in the cost of entire therapeutic treatments coupled with increased therapy efficiency.

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“…Accordingly, the appearance of PS in the outer membrane leaflet is a signal of synaptosomal apoptosis, which was also observed in brain post-mortem autopsies of patients with mild cognitive impairment and AD [39]. Next to the PS distribution, also its overall level is likely to have an impact: In PC12 cells with induced apoptosis, a reduction in the level of PS was detectable before the detection of apoptosis [40].…”

Section: Discussionmentioning

confidence: 85%

Soy Lecithin-Derived Phosphatidylserine Plus Phosphatidic Acid: Effects on Brain Functions in Elderly Patients with Alzheimer's Disease and Dementia

Moré¹,

Rutenberg²

2017

J Aging Sci

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Phosphatidic acid (PA) and phosphatidylserine (PS) and are natural constituents of healthy brain cell membranes, which have been recognized since the 1970s as essential to normal neuronal functioning. PA is a precursor in the formation of other phospholipids, including PS and phosphatidylethanolamine (PE). Also, it has an impact on membrane rigidity/flexibility, which is important in modulating exo-and endocytosis. PS is also an important precursor for PE synthesis. Since PS predominantly occurs in brain cells, but normal diets do not include the consumption of brains, PS is available to our brains mostly via natural "production" in our bodies.Here, we present a tabulated literature survey of clinical studies on PS and/or PA regarding brain function in elderly people. In addition we give a summary on two of our our already published pilot studies performed with a brain-health food supplement containing a proprietary blend of 100 mg PS and 80 mg PA produced from soy lecithin: A three-month double-blind, placebo-controlled study demonstrated the positive influence of three PS+PA capsules/ day, (300 mg PS+240 mg PA per day; n=40)) or placebo (n=32) on memory and mood in functioning, non-depressive elderly people with memory problems. In a two-month randomized, double-blind, placebo-controlled study, three PS+PA capsules/day (300 mg PS+240 mg PA per day; n=56) or placebo (n=40) improved daily functioning, mental health, emotional state, and self-reported general condition in patients with Alzheimer's disease (AD).Altogether there is encouraging clinical data that PS+PA supplementation could be beneficial to AD patients and other elderly people with memory or cognition problems. Long-term studies are, however, still lacking. Keywords: Phosphatidylserine (PS) and Phosphatidic Acid (PA) in MemoryThe membrane phospholipids phosphatidic acid (PA) and phosphatidylserine (PS) are essential to cellular functioning, acting as a biological detergent, keeping fatty substances soluble and cell membranes flexible [1,2]. During the pathogenesis of several age-related neurodegenerative diseases, including Alzheimer's disease, the neuronal membrane lipid composition is altered in the brain [3,4]. Also, the lipid raft composition appears to be altered in neurodegenerative diseases [5]. PS (and PA), produced by enzymatic conversion of soybean lecithin, avoids possible regulatory and safety issues regarding bovine spongiform encephalopathy. Soy lecithin-derived PS is absorbed and metabolized, with elevated serum levels for at least 1.5 hours after an oral dose, as has been shown within a kinetic study on 8 human volunteers. The baseline serum level of PS in relation to the level of total serum phospholipids was around 2%. 30 minutes after ingestion, it started to increase, peaking at 90 minutes after intake at around 4%, and returning to the basal level 180 minutes after intake [23].Recently, oral administration of phosphatidylcholine/phosphatidylethanolamine (PE) -transphosphatidylated PS has been shown to improve memory imp...

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Changes in Lipid Composition During Manganese-Induced Apoptosis in PC12 Cells

Cited by 9 publications

References 55 publications

Manganese promotes intracellular accumulation of AQP2 via modulating F-actin polymerization and reduces urinary concentration in mice

Manganese promotes intracellular accumulation of AQP2 via modulating F-actin polymerization and reduces urinary concentration in mice

Exogenous Fatty Acids Modulate ER Lipid Composition and Metabolism in Breast Cancer Cells

Soy Lecithin-Derived Phosphatidylserine Plus Phosphatidic Acid: Effects on Brain Functions in Elderly Patients with Alzheimer's Disease and Dementia

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