Task Solutions-Roles of the Enzyme Phospholipase A2 -IIA: BIO3019

Preview text

Running head: Integrative Pathology
Integrative Pathology
Name of the Student
Name of the University
Author Note
1 Integrative Pathology
Abstract
The aim of the paper is to discuss the physiological and pathological roles of the enzyme
phospholipase A2 -IIA in human biology. The secreted phospholipase A2 -IIA forms ester
bonds with the help of a natural phospholipid substrate. The identified secreted
phospholipases A2 have asignificant role in the pathophysiological process which includes
inflammation and cancer. About 1/3rd of the genes which belong to secreted PLA2 contain
disulphide rich low molecular weight enzymes with CA2++ dependence. sPLA2-IIA plays an
essential part in the neurotransmission in the central nervous system and the neurogenesis in
the peripheral nervous system. In the human being, the sPLA2-IIA is the result of the
PLA2G2A at the chromosomal regions of the 1p35-1p36 region. The enzymes by sPLA2-IIA
is usually secreted from the lacrimal glands and the conjunctival epithelia. The paper
discusses the mechanisms and the importance of the physiological functions of the sPLA2-
IIA. Further, the paper explains the mechanisms and pathways of the complication caused
due to sPLA2-IIA. The mechanism mediated by the sPLA2-IIA and the pathology associated
is also described in the paper. The inhibition pathway is also discussed in the paper.
2 Integrative Pathology
Table of Contents
•Introduction …………………………………………………………………………………………………………….. 3
•Discussion ………………………………………………………………………………………………………………. 3
a. Physiological functions of sPLA2-IIA ……………………………………………………………………. 3
b. sPLA2-IIA mediated inflammatory pathology ………………………………………………………… 4
c. Other mechanisms of sPLA2-IIA mediated pathology ……………………………………………… 5
d. Controlling sPLA2-IIA mediated pathology …………………………………………………………… 6
•Conclusion ………………………………………………………………………………………………………………. 6
•References (Harvard referencing) ………………………………………………………………………………. 8
3 Integrative Pathology
•Introduction
The secreted phospholipases A2 (sPLA2) are extracellular enzymes with catalytic
actions (Kitsiouli et al. 2021 ). The hydrolysis of the sn-2 positions of the membrane
glycerophospholipids is discharged the fatty acids and phospholipids. Therefore, regulating
the several associated processes that include the production of the lipid mediators. As of the
current date only 12 mammalian secreted phospholipases A2 were identified. The identified
secreted phospholipases A2 have a significant function in the pathophysiological process
which includes inflammation and cancer (Casale et al.2021 ). The effect of the sPLA2 is not
specifically related to the enzymatic activity, it is also linked with the ability to activate the
target cells with the help of the engagement of the different targets.
The secreted phospholipases A2 (sPLA2) provided several biological functions
among human beings. In a human being, there are nine different members of sPLA2 are
present. They take part in various functions which are hydrolytic activity, tissue distribution
and phospholipid substrate.
The function of Phospholipid A2 plays an essential role in diverse cellular responses,
which include phospholipid digestion, signal transduction, host defence and metabolism (Wu,
Li and Huang 2021 ).It provided precursors for the generation of eicosanoids. It also regulates
the overproduction of the lipid mediators which causes inflammation and tissue disorders.
•Discussion
a. Physiological functions of sPLA2-IIA
The secreted phospholipase A2 (sPLA2) is the family which participates in the
pathological events. The events such as inflammation and atherosclerosis are dependable on
the high and constitutive expressions of the sPLA2 in the areas such as the gastrointestinal
tract, peripheral neurons and gastrointestinal tract (van Hensbergen et al. 2020 ). About 1/3 rd
4 Integrative Pathology
of the genes which belong to secreted PLA2 contain disulphide rich low molecular weight
enzymes with CA2++ dependence. sPLA2-IIA have an important function in the the
neurotransmission in the central nervous system and the neurogenesis in the peripheral
nervous system. The sPLA2-IIA is linked with neurodegenerative diseases. The most
common are the Alzheimer â€sdisease and also cerebrovascular disease. The pathology of
Alzheimer â€sdisease and stroke are related to dementia. The excess calcium influx into the
neurons via L-type voltage-dependent Ca2+ channels intercede 2 sPLA2-induced apoptosis
(Hopp 2021 ). The elevated concentration of the Ca2+ activates the PKC, MAPK and the
cytosolic PLA2. The production of the oxygen species and apoptosis is with the help of
NADPH oxidase which is activated during the process. The activation of PLA2 also releases
the arachidonic acid. These are the physiological functions of sPLA2-IIA in the human body.
b. sPLA2-IIA mediated inflammatory pathology
The function of phospholipase A2-IIA (sPLA2-IIA) have an important role in the
inflammatory pathway. The secretory role of the sPLA2-IIA are in the family of the enzymes
that generate the pro-inflammatory of the lipid mediators which include the production of the
free arachidonic acid (AA) and the Lysophospholipids (Giresha 2021 ). In the human being,
the sPLA2-IIA is the result of the PLA2G2A at the chromosomal regions of the 1p35-1p36
region. This group can be considered under the subgroup of acute-phase proteins that trigger
the inflammatory response to infections with pro-inflammatory metabolites known as
arachidonic acid. Phospholipase A2-IIA acts as amediator and catalyses the release of the
arachidonic acid from the membranes of the phospholipids. This is initiating the synthesis of
the prostaglandins and leukotrienes. This is constantly causing numerous physiological
responses such as vasodilation, chemotaxis and platelet aggregation. The group
Phospholipase A2 (sPLA2-IIA) is linked with the sepsis pathway. The secretion of
Phospholipase A2 (sPLA2-IIA) is connected with the interleukin and tumour necrosis factor
5 Integrative Pathology
(Dore and Boilard 2019 ). These are the essential factors in the process of neutrophil adhesion
and as well as migration.
c. Other mechanisms of sPLA2-IIA mediated pathology
sPLA2-IIA has several functions and role in numerous non-ocular inflammatory
diseases. The increased level of sPLA2-IIA detected in rheumatoid arthritis and inflammatory
bowel disease, acute chest syndrome and septic shock. Zhang et al. (2018) conducted astudy
on the rabbit that showed a significant inflammatory and arthritogenic response. This
experiment suggested that exacerbating role is played by sPLA2-IIA in the synovial fluid.
The inflammation is caused by the ocular surface. The condition of dry eyes is increased in
the patients who showed an increase in sPLA2-IIA than the patients with anormal level. The
sPLA2-IIA also stimulate the release of the PGE2. The prostaglandin E2 (PGE2) is atype of
lipid molecule that causes the release of hormone-like effects in the human body (Smeitink et
al.2020 ). The sPLA2-IIA also causes the stimulation of inflammatory cytokines in the ocular
surface of the epithelial corneal and other conjunctival cells. The stimulation activity
discussed above is more amplified during the time the cell or tissue was pre-compromised
with the desiccation, TNF- αand IL-1 β.
In the study conducted by Wei and Asbell (2020) discussed that among the patients
with dry eyes, the production of the tears is significantly reduced. The positive feedback loop
influences the levels of the sPLA2-IIa. The eicosanoids which influence the sPLA2-IIa level
cause the release of the cytokines such as TNF- α and IL-1 β mentioned above. A dry eye
condition is aform of chronic eye condition present in the ocular surface inflammation. The
ocular surface inflammation mediators which include cytokines, HLA-DR, chemokines and
the PGE2 are released by the sPLA2-IIa.
6 Integrative Pathology
d. Controlling sPLA2-IIA mediated pathology
Non-steroidal anti-inflammatory drugs are the type of drugs which are most
commonly prescribed for the ocular inflammatory condition (Al-Lawati, Binkhathlan and
Lavasanifar, 2019 ). This drug inhibits the cyclooxygenase which suppresses the metabolism
of arachidonic acid and synthesis of the prostaglandins. There is a strong possibility of
corneal melting and perforation due to use the of NSAIDs commonly after the ocular surgery.
This is commonly seen in patients with or without systematic diseases such as Sjogren
syndrome, rosacea and rheumatoid arthritis. Since NSAIDs inhibit the functioning of COX-1
and COX-2. This has no effect on Leukotrienes and PAF (Khan et al. 2022 ). The inhibition
of the sPLA2-IIA provided abetter solution and blocks the production of other inflammatory
substances. A small molecule with inhibitory action specific to the human sPLA2-IIA was
created for the active site of the human non-pancreatic enzyme with the help of tight-binding
interactions. Many studies were conducted on the sPLA2 inhibitor. The action of this
inhibitor was to optimise the Varespladib sodium to five to ten levels less active (Alangode,
Reick and Reick, 2020 ). Varespladib non-specifically binds to non-specifically higher levels
of the protein before the reaching the catalytic site for better inhibition.
•Conclusion
From the above analysis, it can be concluded that the secreted phospholipases A2
(sPLA2) are extracellular enzymes with catalytic actions. The hydrolysis of the sn- 2
positions of the membrane glycerophospholipids is to release the fatty acids and
phospholipids. The secreted phospholipases A2 (sPLA2) provided several biological
functions among human beings. The function of Phospholipid A2 plays an essential role in
diverse cellular responses, which include phospholipid digestion, signal transduction, host
defence and metabolism. The secreted phospholipase A2 (sPLA2) is the family which
participates in the pathological events. The events such as inflammation and atherosclerosis
7 Integrative Pathology
are dependable on the high and constitutive expressions of the sPLA2 in the areas such as the
gastrointestinal tract, peripheral neurons and gastrointestinal tract. The pathology of
Alzheimer â€sdisease and stroke are related to dementia. The excess calcium influx into the
neurons via L-type voltage-dependent Ca2+ channels intercede 2 sPLA2-induced apoptosis.
The group Phospholipase A2 (sPLA2-IIA) is linked with sepsis pathway and also have
inflammatory pathway. The secretion of Phospholipase A2 (sPLA2-IIA) is associated with
the interleukin and tumour necrosis factor. The increased level of sPLA2-IIA in the inflamed
tissues or serum is detected in rheumatoid arthritis and inflammatory bowel disease, acute
chest syndrome and septic shock. Non-steroidal anti-inflammatory drugs are prescribed drugs
for the ocular inflammatory condition. The inhibition of the sPLA2-IIA provides a better
solution and blocks the production of other inflammatory substances.
8 Integrative Pathology
•References (Harvard referencing)
Alangode, A., Reick, M. and Reick, M., 2020. Sodium oleate, arachidonate, and linoleate
enhance fibrinogenolysis by Russell’s viper venom proteinases and inhibit FXIIIa; arole for
phospholipase A2 in venom induced consumption coagulopathy. Toxicon, 186, pp.83-93.
Al-Lawati, H., Binkhathlan, Z. and Lavasanifar, A., 2019. Nanomedicine for the effective
and safe delivery of non-steroidal anti-inflammatory drugs: A review of preclinical research.
European Journal of Pharmaceutics and Biopharmaceutics, 142, pp.179-194.
Casale, J., Kacimi, S.E.O. and Varacallo, M., 2021. Biochemistry, phospholipase A2. In
StatPearls [Internet]. StatPearls Publishing.
Dore, E. and Boilard, E., 2019. Roles of secreted phospholipase A2 group IIA in
inflammation and host defense. Biochimica et Biophysica Acta (BBA)-Molecular and Cell
Biology of Lipids, 1864(6), pp.789-802.
Giresha, A.S., 2021. Secretory phospholipase A2 Group IIA: A Potential Therapeutic Target
in Inflammation. Current Research and Trends in Medical Science and Technology, p.34.
Hopp, S.C., 2021. Targeting microglia L‐type voltage ‐dependent calcium channels for the
treatment of central nervous system disorders. Journal of Neuroscience Research, 99(1),
pp.141-162.
Khan, H., Sharma, K., Kumar, A., Kaur, A. and Singh, T.G., 2022. Therapeutic implications
of cyclooxygenase (COX) inhibitors in ischemic injury. Inflammation Research, pp.1-16.
Kitsiouli, E., Tenopoulou, M., Papadopoulos, S. and Lekka, M.E., 2021. Phospholipases A2
as biomarkers in ARDS. Biomedical Journal.
9 Integrative Pathology
Smeitink, J., Jiang, X., Pecheritsyna, S., Renkema, H., van Maanen, R. and Beyrath, J., 2020.
Hypothesis: mPGES-1-derived prostaglandin E2, a so far missing link in COVID-19
pathophysiology?.
van Hensbergen, V.P., Wu, Y., van Sorge, N.M. and Touqui, L., 2020. Type IIA secreted
phospholipase A2 in host defense against bacterial infections. Trends in immunology, 41(4),
pp.313-326.
Wu, W., Li, W.X. and Huang, C.H., 2021. Phospholipase A2, a nonnegligible enzyme
superfamily in gastrointestinal diseases. Biochimie.
Wei, Y. and Asbell, P.A., 2020. sPLA2-IIa participates in ocular surface inflammation in
humans with dry eye disease. Experimental Eye Research, 201, p.108209.
Zhang, Q., Dehaini, D., Zhang, Y., Zhou, J., Chen, X., Zhang, L., Fang, R.H., Gao, W. and
Zhang, L., 2018. Neutrophil membrane-coated nanoparticles inhibit synovial inflammation
and alleviate joint damage in inflammatory arthritis. Nature nanotechnology, 13(12),
pp.1182-1190.