Modification of intracellular free calcium in cultured A10 vascular smooth muscle cells by exogenous phosphatidic acid

Bhugra, Praveen; Xu, Yan‐Jun; Rathi, Satyajeet S.; Dhalla, Naranjan S.

doi:10.1016/s0006-2952(03)00201-6

Cited by 7 publications

(4 citation statements)

References 36 publications

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“…The current study is a significant step to advance FASD research, as the data clearly demonstrates that in vivo PA supplementation along with alcohol would effectively prevent alcohol-induced uterine artery dysfunction. In support of our findings, outside the FASD field, PA has been reported to play a role in arterial function [71][72][73].…”

Section: Alcohol-induced Uterine Artery Dysfunction and Its Reversal ...supporting

confidence: 91%

In Vivo Administration of Phosphatidic Acid, a Direct Alcohol Target Rescues Fetal Growth Restriction and Maternal Uterine Artery Dysfunction in Rat FASD Model

Janeski,

Naik,

Carabulea

et al. 2024

Nutrients

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Fetal growth restriction is a hallmark of Fetal Alcohol Syndrome (FAS) and is accompanied by maternal uterine circulatory maladaptation. FAS is the most severe form of Fetal Alcohol Spectrum Disorder (FASD), a term for the range of conditions that can develop in a fetus when their pregnant mother consumes alcohol. Alcohol exerts specific direct effects on lipids that control fundamental developmental processes. We previously demonstrated that direct in vitro application of phosphatidic acid (PA, the simplest phospholipid and a direct target of alcohol exposure) to excised uterine arteries from alcohol-exposed rats improved vascular function, but it is unknown if PA can rescue end organ phenotypes in our FASD animal model. Pregnant Sprague-Dawley rats (n = 40 total dams) were gavaged daily from gestational day (GD) 5 to GD 19 with alcohol or maltose dextrin, with and without PA supplementation, for a total of four unique groups. To translate and assess the beneficial effects of PA, we hypothesized that in vivo administration of PA concomitant with chronic binge alcohol would reverse uterine artery dysfunction and fetal growth deficits in our FASD model. Mean fetal weights and placental efficiency were significantly lower in the binge alcohol group compared with those in the control (p < 0.05). However, these differences between the alcohol and the control groups were completely abolished by auxiliary in vivo PA administration with alcohol, indicating a reversal of the classic FAS growth restriction phenotype. Acetylcholine (ACh)-induced uterine artery relaxation was significantly impaired in the uterine arteries of chronic in vivo binge alcohol-administered rats compared to the controls (p < 0.05). Supplementation of PA in vivo throughout pregnancy reversed the alcohol-induced vasodilatory deficit; no differences were detected following in vivo PA administration between the pair-fed control and PA alcohol groups. Maximal ACh-induced vasodilation was significantly lower in the alcohol group compared to all the other treatments, including control, control PA, and alcohol PA groups (p < 0.05). When analyzing excitatory vasodilatory p1177-eNOS, alcohol-induced downregulation of p1177-eNOS was completely reversed following in vivo PA supplementation. In summary, these novel data utilize a specific alcohol target pathway (PA) to demonstrate a lipid-based preventive strategy and provide critical insights important for the development of translatable interventions.

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Section: Alcohol-induced Uterine Artery Dysfunction and Its Reversal ...supporting

confidence: 91%

In Vivo Administration of Phosphatidic Acid, a Direct Alcohol Target Rescues Fetal Growth Restriction and Maternal Uterine Artery Dysfunction in Rat FASD Model

Janeski,

Naik,

Carabulea

et al. 2024

Nutrients

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“…Work with many cell types (Bhugra et al, 2003; Dhalla et al, 1997; Liu et al, 1999; Siddiqui and English, 1997, 2000) has shown that addition of ~50–100 μM dicapryloyl PA (dPA) elevated [Ca] i . Thus, we added dPA to Xenopus eggs and found that the lipid induced [Ca] i -dependent fertilization events (e.g., cortical contraction and gravitational rotation, a measure of cortical granule exocytosis) had an IC50 of ~100 μM and maximal response was achieved by 400 μM PA (data not shown).…”

Section: Resultsmentioning

confidence: 99%

Activation of Src and release of intracellular calcium by phosphatidic acid during Xenopus laevis fertilization

Bates

Fees

Holland

et al. 2014

Developmental Biology

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We report a new step in the fertilization in Xenopus laevis which has been found to involve activation of Src tyrosine kinase to stimulate phospholipase C-γ (PLC- γ) which increases inositol 1,4,5-trisphosphate (IP3) to release intracellular calcium ([Ca]i). Molecular species analysis and mass measurements suggested that sperm activate phospholipase D (PLD) to elevate phosphatidic acid (PA). We now report that PA mass increased 2.7 fold by 1 minute after insemination and inhibition of PA production by two methods inhibited activation of Src and PLCγ, increased [Ca]i and other fertilization events. As compared to 14 other lipids, PA strongly bound Xenopus Src but not PLCγ. Addition of synthetic PA activated egg Src (an action requiring intact lipid rafts) and PLCγ as well as doubling the amount of PLCγ in rafts. In the absence of elevated [Ca]i, PA addition elevated IP3 mass to levels equivalent to that induced by sperm (but twice that achieved by calcium ionophore). Finally, PA induced [Ca]i release that was blocked by an IP3 receptor inhibitor. As only PLD1b message was detected, and Western blotting did not detect PLD2, we suggest that sperm activate PLD1b to elevate PA which then binds to and activates Src leading to PLCγ stimulation, IP3 elevation and [Ca]i release. Due to these and other studies, PA may also play a role in membrane fusion events such as sperm-egg fusion, cortical granule exocytosis, the elevation of phosphatidylinositol 4,5-bisphosphate and the large, late increase in sn 1,2-diacylglycerol in fertilization.

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“…PA addition to vascular smooth muscle elevated [Ca +2 ] i and this elevation was blocked by the PLC inhibitor U73122 or an IP 3 receptor blocker (Bhugra et al, 2003). In rat neonatal cardiomyocytes, PA (but not LPA) increased IP 3 mass and [Ca +2 ] i , and PA action was blocked by PLC inhibitor U73122 (inactive U73343 and a PKC inhibitor did not) (Liu et al, 1999).…”

Section: Regulation Of Xenopus Fertilization Through Multiple Lipid Pmentioning

confidence: 99%

Phospholipase C and D regulation of Src, calcium release and membrane fusion during Xenopus laevis development

Stith

2015

Developmental Biology

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This review emphasizes how lipids regulate membrane fusion and the proteins involved in three developmental stages: oocyte maturation to the fertilizable egg, fertilization and during first cleavage. Decades of work show that phosphatidic acid (PA) releases intracellular calcium, and recent work shows that the lipid can activate Src tyrosine kinase or phospholipase C during Xenopus fertilization. Numerous reports are summarized to show three levels of increase in lipid second messengers inositol 1,4,5-trisphosphate and sn 1,2-diacylglycerol (DAG) during the three different developmental stages. In addition, possible roles for PA, ceramide, lysophosphatidylcholine, plasmalogens, phosphatidylinositol 4-phosphate, phosphatidylinositol 5-phosphate, phosphatidylinositol 4,5-bisphosphate, membrane microdomains (rafts) and phosphatidylinositol 3,4,5-trisphosphate in regulation of membrane fusion (acrosome reaction, sperm-egg fusion, cortical granule exocytosis), inositol 1,4,5-trisphosphate receptors, and calcium release are discussed. The role of six lipases involved in generating putative lipid second messengers during fertilization is also discussed: phospholipase D, autotaxin, lipin1, sphingomyelinase, phospholipase C, and phospholipase A2. More specifically, proteins involved in developmental events and their regulation through lipid binding to SH3, SH4, PH, PX, or C2 protein domains is emphasized. New models are presented for PA activation of Src (through SH3, SH4 and a unique domain), that this may be why the SH2 domain of PLCγ is not required for Xenopus fertilization, PA activation of phospholipase C, a role for PA during the calcium wave after fertilization, and that calcium/calmodulin may be responsible for the loss of Src from rafts after fertilization. Also discussed is that the large DAG increase during fertilization derives from phospholipase D production of PA and lipin dephosphorylation to DAG.

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Modification of intracellular free calcium in cultured A10 vascular smooth muscle cells by exogenous phosphatidic acid

Cited by 7 publications

References 36 publications

In Vivo Administration of Phosphatidic Acid, a Direct Alcohol Target Rescues Fetal Growth Restriction and Maternal Uterine Artery Dysfunction in Rat FASD Model

In Vivo Administration of Phosphatidic Acid, a Direct Alcohol Target Rescues Fetal Growth Restriction and Maternal Uterine Artery Dysfunction in Rat FASD Model

Activation of Src and release of intracellular calcium by phosphatidic acid during Xenopus laevis fertilization

Phospholipase C and D regulation of Src, calcium release and membrane fusion during Xenopus laevis development

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