Activation of phospholipase D by ADP-ribosylation factor in rat submandibular acinar cells

Li, Liang; Mellow, L; Bhullar, Rajinder P.; Fleming, Norman

doi:10.1016/s0003-9969(98)00007-7

Cited by 8 publications

(16 citation statements)

References 27 publications

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“…Consistent with our previous observation [10], AlF 4 − , a widely used activator of heterotrimeric GTP‐binding proteins, stimulated PLD to around four‐fold control levels in intact rat submandibular acinar cells. This effect was dependent on aluminum ion concentration, with a maximal response at 3 mM NaF/2 μM AlCl 3 (Fig.…”

Section: Resultssupporting

confidence: 92%

“…The stimulatory effect of AlF 4 − on PLD was blocked by the aluminum ion chelator deferoxamine (data not shown). From our previous studies on this model, it is assumed that activation of PLD by aluminum fluoride in intact cells results from a stimulatory effect on a heterotrimeric GTP‐binding protein [4,10].…”

Section: Resultsmentioning

confidence: 99%

“…The assays were conducted at 37°C for 20 min in a total assay volume of 60 μl. The reaction was stopped, PEth was extracted and quantified as described previously [10]. PLD assays in cells permeabilized by 50 μg/ml digitonin and in intact cells were conducted by labeling the cellular phospholipids with [ 3 H]AA and measuring radiolabeled PEth formation [10].…”

Section: Methodsmentioning

confidence: 99%

“…Arf translocation was determined in a permeabilized cell system by an immunoblotting technique as described previously [10]. A polyclonal anti‐Arf antibody was kindly provided by Dr. R. Bhullar, University of Manitoba.…”

Section: Methodsmentioning

confidence: 99%

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Aluminum fluoride inhibits phospholipase D activation by a GTP‐binding protein‐independent mechanism

Li¹,

Fleming²

1999

FEBS Letters

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Aluminum fluoride (AlF 3 4 ) inhibited guanine nucleotide-activated phospholipase D (PLD) in rat submandibular gland cell-free lysates in a concentration-dependent response. This effect was consistent in permeabilized cells with endogenous phospholipid PLD substrates. Inhibition was not caused by either fluoride or aluminum alone and was reversed by aluminum chelation. Inhibition of PLD by aluminum fluoride was not mediated by cAMP, phosphatases 1, 2A or 2B, or phosphatidate phosphohydrolase. AlF 3 4 had a similar inhibitory effect on rArfstimulated PLD, but did not block the translocation of Arf from cytosol to membranes, indicating a post-GTP-binding-protein site of action. Oleate-sensitive PLD, which is not guanine nucleotide-dependent, was also inhibited by AlF 3 4 , supporting a G protein-independent mechanism of action. A submandibular Golgi-enriched membrane preparation had high PLD activity which was also potently inhibited by AlF 3 4 , leading to speculation that the known fluoride inhibition of Golgi vesicle transport may be PLD-mediated. It is proposed that aluminum fluoride inhibits different forms of PLD by a mechanism that is independent of GTP-binding proteins and that acts via a membrane-associated target which may be the enzyme itself.z 1999 Federation of European Biochemical Societies.

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Section: Resultssupporting

confidence: 92%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Aluminum fluoride inhibits phospholipase D activation by a GTP‐binding protein‐independent mechanism

Li¹,

Fleming²

1999

FEBS Letters

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“…Such AlF 4 inhibitory effect was confirmed in permeabilized cells in a concentration-dependent manner [95]. It is known that PLD stimulation with ARF/GTP--S involves ARF translocation from cytosol to membranes [96]. In submandibular membranes, however, AlF 4 inhibited rARF-stimulated PLD without blocking ARF translocation to membranes.…”

Section: Mysterious Inhibitorsmentioning

confidence: 67%

Phospholipase D Inhibition: Beneficial and Harmful Consequences for a Double-Dealer Enzyme

Auricchio¹,

D'Aquilio²,

Chiurchiù³

et al. 2007

CEI

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One of the most promising strategies for drug design and development is the identification of new molecules able to selectively inhibit those enzymes involved in pathological processes, without affecting other enzymes associated with physiological functions. Nevertheless, some enzymes can show a double-edge aspect of their own inhibition, which can lead to positive as well as negative consequences according to the pathological state. Phospholipase D (PLD), an ubiquitous enzyme nowadays considered as a critical regulator of several aspects of cell biology and signal transduction pathways, is a clear example of those double-dealer enzymes. While a great deal has been learned about PLD structure, biological functions and activation/regulation mechanisms, little yet is known about the derivable effects of its potential negative regulation, also due to the lack of specific inhibitors. Multiple evidences on PLD involvement in many pathological states development and progression, including inflammation, carcinogenesis and metastases, have been supplied, so that a deregulation of its activity could contribute to attenuate or slow down the inflammatory and tumour formation/progression processes. On the other hand, in agreement with other previous observations, we have recently demonstrated the direct contribution of PLD activation in promoting intracellular mycobacterial killing. In this case, PLD inhibition resulted in a significant reduction of antimicrobial innate immune response and, hence, in a possible harmful effect. In the light of the above reported considerations, besides the recent advances in characterising new compounds able to selectively inhibit PLD activity and/or signalling, this review aimed at elucidating the potential dual beneficial/harmful consequences of PLD activity modulation.

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Localization of phospholipid-related signal molecules in salivary glands of rodents: A review

Hipkaeo

Kondo

2023

Journal of Oral Biosciences

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Activation of phospholipase D by ADP-ribosylation factor in rat submandibular acinar cells

Cited by 8 publications

References 27 publications

Aluminum fluoride inhibits phospholipase D activation by a GTP‐binding protein‐independent mechanism

Aluminum fluoride inhibits phospholipase D activation by a GTP‐binding protein‐independent mechanism

Phospholipase D Inhibition: Beneficial and Harmful Consequences for a Double-Dealer Enzyme

Localization of phospholipid-related signal molecules in salivary glands of rodents: A review

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