Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
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Target Concepts:
Gene/Protein
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Query: UNIPROT:P00750 (
PLA
)
16,800
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The skin represents one of the tissues that are most profoundly influenced by alterations in the quality of lipids (lipoquality). Lipids not only constitute cellular membranes, but also serve as bioactive lipid mediators and essential components of the skin barrier. Phospholipase A
2
(
PLA
2
) enzymes supply fatty acids and lysophospholipids from membrane phospholipids, thereby variably affecting cutaneous homeostasis. Accordingly, perturbation of particular
PLA
2
-driven lipid pathways can be linked to various forms of skin disease. In this review article, we highlight the roles of several
PLA
2
subtypes in cutaneous pathophysiology, as revealed by transgenic/knockout studies in combination with comprehensive lipidomics. We focus mainly on secreted
PLA
2
group IIF (sPLA
2
-IIF), which is associated with epidermal hyperplasia through mobilization of a unique lipid metabolite. We also address the distinct roles of sPLA
2
-IIE in hair follicles and sPLA
2
-IID in lymphoid immune cells that secondarily affect cutaneous inflammation, and provide some insights into species differences in sPLA
2
s. Additionally, we briefly overview the patatin-like phospholipase
PNPLA1
, which belongs to the Ca
2+
-independent
PLA
2
(iPLA
2
) family, as a key regulator of skin barrier function through catalysis of a unique non-
PLA
2
reaction. These knowledges on lipid metabolism driven by various
PLA
2
subtypes will open novel opportunities for translated studies toward diagnosis and therapy of human skin diseases.
...
PMID:Phospholipase A
2
in skin biology: new insights from gene-manipulated mice and lipidomics. 3054 11
Patatin-like phospholipases (PNPLAs) are highly conserved enzymes of prokaryotic and eukaryotic organisms with major roles in lipid homeostasis. The genome of the malaria parasite Plasmodium falciparum encodes four putative PNPLAs with predicted functions during phospholipid degradation. We here investigated the role of one of the plasmodial PNPLAs, a putative
PLA
2
termed
PNPLA1
, during blood stage replication and gametocyte development.
PNPLA1
is present in the asexual and sexual blood stages and here localizes to the cytoplasm.
PNPLA1
-deficiency due to gene disruption or conditional gene-knockdown had no effect on intraerythrocytic growth, gametocyte development and gametogenesis. However, parasites lacking
PNPLA1
were impaired in gametocyte induction, while
PNPLA1
overexpression promotes gametocyte formation. The loss of
PNPLA1
further leads to transcriptional down-regulation of genes related to gametocytogenesis, including the gene encoding the sexual commitment regulator AP2-G. Additionally, lipidomics of
PNPLA1
-deficient asexual blood stage parasites revealed overall increased levels of major phospholipids, including phosphatidylcholine (PC), which is a substrate of
PLA
2
. PC synthesis is known to be pivotal for erythrocytic replication, while the reduced availability of PC precursors drives the parasite into gametocytogenesis; we thus hypothesize that the higher PC levels due to
PNPLA1
-deficiency prevent the blood stage parasites from entering the sexual pathway.
...
PMID:A patatin-like phospholipase functions during gametocyte induction in the malaria parasite Plasmodium falciparum. 3173 53
