Involvement of thiol groups in the impairment of cardiac sarcoplasmic reticular phospholipase D activity by oxidants

Dai, Jian; Meij, Johanna T. A.; Dhalla, Vikram; Panagia, Vincenzo

doi:10.1016/0929-7855(94)00031-7

Cited by 13 publications

(3 citation statements)

References 31 publications

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“…Like the kinase pathways activated during I/R and serving protective functions [67, 116–119], there is considerable evidence that oxidative stress activates and regulates PLD activity [120–126]. Activation of PLD in response to oxidative stress is associated with various cardiac pathologies, including coronary heart diseases [127–129].…”

Section: Rhoa and Phospholipid Signalingmentioning

confidence: 99%

Revisited and Revised: Is RhoA Always a Villain in Cardiac Pathophysiology?

Miyamoto

Xiang

et al. 2010

J. of Cardiovasc. Trans. Res.

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The neonatal rat ventricular myocyte model of hypertrophy has provided tremendous insight with regard to signaling pathways regulating cardiac growth and gene expression. Many mediators thus discovered have been successfully extrapolated to the in vivo setting, as assessed using genetically engineered mice and physiological interventions. Studies in neonatal rat ventricular myocytes demonstrated a role for the small G-protein RhoA and its downstream effector kinase, Rho-associated coiled-coil containing protein kinase (ROCK), in agonist-mediated hypertrophy. Transgenic expression of RhoA in the heart does not phenocopy this response, however, nor does genetic deletion of ROCK prevent hypertrophy. Pharmacologic inhibition of ROCK has effects most consistent with roles for RhoA signaling in the development of heart failure or responses to ischemic damage. Whether signals elicited downstream of RhoA promote cell death or survival and are deleterious or salutary is, however, context and cell-type dependent. The concepts discussed above are reviewed, and the hypothesis that RhoA might protect cardiomyocytes from ischemia and other insults is presented. Novel RhoA targets including phospholipid regulated and regulating enzymes (Akt, PI kinases, phospholipase C, protein kinases C and D) and serum response element-mediated transcriptional responses are considered as possible pathways through which RhoA could affect cardiomyocyte survival.

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Section: Rhoa and Phospholipid Signalingmentioning

confidence: 99%

Revisited and Revised: Is RhoA Always a Villain in Cardiac Pathophysiology?

Miyamoto

Xiang

et al. 2010

J. of Cardiovasc. Trans. Res.

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“…While both SL and SR PLD activities, in vitro, have been reported to be inhibited by oxidants such as H 2 O 2 and HOCl, through reversible modification of associated thiol groups [108,109], some of the inconsistencies between the observations in the isolated perfused heart and oxidant effects on SR and SL preparations could be explained on the basis that the functional thiol groups of the SL PLD2 in the isolated perfused heart are not as readily accessible by oxidants as these are in the isolated SL preparation. Such responses may also be due to differences in the sensitivity of the SR and SL PLD to different concentrations of oxidant molecules as well as ROS.…”

Section: Pimentioning

confidence: 99%

Phospholipid-mediated signaling in diseased myocardium

et al. 2006

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“…The oxidative stress causes a profound change in the cardiomyocyte redox state ( 56 ). For the phospholipase D family member PLD2, an important signaling enzyme in mammalian cells, the oxidation state of its thiol groups by oxidants has a significant effect on the PLD activity and subsequent signal transduction process that influences cardiomyocyte function ( 54 , 57 ). The functional relevance of the OCS300 oxidation in hPLD3 is not clear, but it may act as a sensor of the hPLD3 redox state level in response to oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

Structural analysis of PLD3 reveals insights into the mechanism of lysosomal 5′ exonuclease-mediated nucleic acid degradation

Roske,

Cappel,

Cremer

et al. 2023

Nucleic Acids Research

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The phospholipase D (PLD) family is comprised of enzymes bearing phospholipase activity towards lipids or endo- and exonuclease activity towards nucleic acids. PLD3 is synthesized as a type II transmembrane protein and proteolytically cleaved in lysosomes, yielding a soluble active form. The deficiency of PLD3 leads to the slowed degradation of nucleic acids in lysosomes and chronic activation of nucleic acid-specific intracellular toll-like receptors. While the mechanism of PLD phospholipase activity has been extensively characterized, not much is known about how PLDs bind and hydrolyze nucleic acids. Here, we determined the high-resolution crystal structure of the luminal N-glycosylated domain of human PLD3 in its apo- and single-stranded DNA-bound forms. PLD3 has a typical phospholipase fold and forms homodimers with two independent catalytic centers via a newly identified dimerization interface. The structure of PLD3 in complex with an ssDNA-derived thymidine product in the catalytic center provides insights into the substrate binding mode of nucleic acids in the PLD family. Our structural data suggest a mechanism for substrate binding and nuclease activity in the PLD family and provide the structural basis to design immunomodulatory drugs targeting PLD3.

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Involvement of thiol groups in the impairment of cardiac sarcoplasmic reticular phospholipase D activity by oxidants

Cited by 13 publications

References 31 publications

Revisited and Revised: Is RhoA Always a Villain in Cardiac Pathophysiology?

Revisited and Revised: Is RhoA Always a Villain in Cardiac Pathophysiology?

Phospholipid-mediated signaling in diseased myocardium

Structural analysis of PLD3 reveals insights into the mechanism of lysosomal 5′ exonuclease-mediated nucleic acid degradation

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