The phospholipases A2 (PLA2s), hydrolyze the sn-2 fatty acid acyl ester bond of phosphoglycerides,
releasing free fatty acids and lysophospholipids. The PLA2s constitute a diverse family of enzymes with
respect to sequence, function, localization, and divalent cation requirements. They play an important role in a
variety of cellular processes, including the digestion and metabolism of phospholipids as well as the
production of precursors for inflammatory reactions. The PLA2s have been classified into at least 5 groups
based on their size, structure, and need for divalent cations . Groups I, II, and III all contain
so-called secreted forms of PLA2, which are extracellular enzymes that have a low molecular mass and
require calcium ions for catalysis, while groups IV and V contain cytosolic forms of PLA2 that have a high
molecular mass and require calcium iron only in the case of group IV PLA2.
General function
Enzyme
Comment
Cellular localization
Cytoplasmic
Comment
Ovarian function
Ovulation, Follicle rupture, Luteolysis
Comment
Kurusu S, et al 1999 reported luteal phospholipase A2 activity increases during functional and
structural luteolysis in pregnant rats.
Phospholipase A2 activity and its
metabolite prostaglandin F2alpha in the corpus luteum remarkably increased just
before parturition and further rose transiently during post-partum structural luteolysis.
The absence of a pups' suckling stimulus delayed corpus luteum involution, being
associated with an altered fluctuation in phospholipase A2 activity and depressed
prostaglandin F2alpha levels. Exogenous prolactin had a reversal effect.
Pharmacological and immunochemical characterization suggests multiple isoforms of
phospholipase A2 in a pregnant corpus luteum. These results show the increased
phospholipase A2 activity and its possible implication in luteolysis in pregnant rats.
Kurusu S, et al 1998 reported the involvement of cytosolic phospholipase A2 in the ovulatory process
in gonadotropin-primed immature rats.
The preovulatory LH surge induces a remarkable increase in ovarian prostaglandins
(PGs) which help to mediate the ovulatory process. The authors investigated whether
cytosolic phospholipase A2 (cPLA2) has a role in this PG production in
PMSG/hCG-primed immature rats. The immunoreactive signal for cPLA2 was
localized in both thecal and granulosa layers of mature follicles and became evident
in response to gonadotropins. The PLA2 activity in the whole ovarian cytosol rose
slightly after PMSG stimulation, persisted relatively constant until 24 h after hCG
injection and thereafter increased gradually. Intra-ovarian bursal injection of
arachidonyl trifluoromethyl ketone, a specific inhibitor for cPLA2 , significantly reduced ovarian PGE2 content and the ovulation rate. These
results suggest that cPLA2 exists in periovulatory follicles and functions in PG
production related to the ovulation process.
Kurusu S, et al reported sustained activity of luteal cytosolic phospholipase A2 during
luteolysis in pseudopregnant rats: its possible implication in tissue
involution.
The authors investigated the expression and activity of cytosolic phospholipase A2 (cPLA2)
in the corpus luteum during spontaneous and induced luteolysis in pseudopregnant
rats. In both models, luteal PLA2 activity rose in association with functional
regression and persisted during the following structural regression. Tissue
concentration of prostaglandin F2alpha with a luteolytic potency showed a similar
fluctuation. The enzyme activity was almost completely suppressed by a
cPLA2-specific inhibitor. Expression of cPLA2, analyzed by immunohistochemistry,
became enhanced during luteolysis with preferential localization to phagocytotic and
fibrotic replacement sites.
Expression regulated by
FSH, LH, Growth Factors/ cytokines
Comment
Kol S, et al 1997 reported that interleukin-1 beta stimulates ovarian phosphoipase A2 (PLA2)
expression and activity and up-regulation of both secretory and
cytosolic PLA2.
Interleukin (IL)-1 beta has been shown to stimulate ovarian prostaglandin
biosynthesis. The authors hypothesized that this effect entails the induction of phospholipase
A2 (PLA2). Treatment of cultured whole ovarian dispersates of immature rat origin
with IL-1 beta produced significant increases in [3H]arachidonic acid (AA) release
and [3H]prostanoid accumulation as well as increases in cellular PLA2 activity and
in secretory PLA2 and cytosolic PLA2 transcripts. Cotreatment with IL-1 receptor
antagonist reversed IL-mediated (and basal) release of [3H]labeled AA and
prostaglandin products, as well as cellular PLA2 activity. Treatment with IL-1 beta
also promoted a significant decrease in the cellular content of [3H]phospholipids
(apparently phosphatidylethanolamine but not phosphatidylcholine). These
observations establish the ovary as a site of IL-1-dependent sPLA2 and cPLA2 gene
expression, document the presence of a possible phosphatidylethanolamine-dependent
PLA2 activity in cultured whole ovarian dispersates, reveal the up-regulatory,
receptor-mediated action of IL-1 beta in this regard and suggest the existence of
endogenous PLA2-stimulating/ IL-1-like bioactivity.
Ovarian localization
Granulosa, Luteal cells
Comment
Kol S, et al reported that glucocorticoids suppress basal (but not interleukin-1-supported)
ovarian phospholipase A2 activity and evidence for glucocorticoid
receptor-mediated regulation.
Kol S, et al 1997 reported studies on the rat ovarian phospholipase A2 system dealing with gene expression, cellular
localization, activity characterization, and interleukin-1 dependence.
Molecular probing of whole ovarian material revealed the immature rat
ovary to be a site of modest secretory PLA2 (sPLA2) gene expression. However, no
change in ovarian sPLA2 gene expression was noted during the periovulatory period.
Comparable probing for cytosolic PLA2 (cPLA2) failed to disclose a quantifiable
signal. However, in situ hybridization localized both sPLA2 and cPLA2 (sPLA2 >
cPLA2) transcripts to the granulosa cell layer of the ovarian follicle. Treatment of
cultured whole ovarian dispersates with IL-1 beta produced significant (P < 0.01)
increments in the steady state levels of transcripts corresponding to both sPLA2
(1.7-fold increase) and cPLA2 (5-fold increase), an effect reversed by an IL-1
receptor antagonist, suggesting mediation via a specific IL-1 receptor. Treatment with aminoguanidine, an inhibitor of inducible
nitric oxide synthase, led to augmentation of the ability of IL-1 beta to up-regulate
sPLA2 and cPLA2 gene expression as well as medium PLA2 activity. Total cellular
PLA2 activity proved time, cell density, and calcium dependent, with an optimal pH
of 8.0-9.0 and K(m) values in the low micromolar range (2-5 microM). The
observations 1) establish the rat ovary as a site of sPLA2 and cPLA2 gene expression,
2) localize the corresponding transcripts to the granulosa cell layer, and 3) establish
IL-1 beta as an up-regulatory agent for ovarian sPLA2 and cPLA2 gene expression as
well as for ovarian PLA2 activity. These findings also indicate that the IL-1 effect is
1) receptor mediated, 2) contingent in part upon de novo protein biosynthesis, and 3)
inhibited by nitric oxide. These observations support the proposition that PLA2 may
be a key component in the IL-1-stimulated biosynthesis of ovarian PGs.