Biomedical Engineering Reference
In-Depth Information
spermatocytes suggesting species-specific differences.
131
If DP8 and DP9 play
crucial roles in the development of sperm maturation, it can be speculated that
loss of both DP8/9 expression within the male reproductive system could lead
to sterility. Future studies analyzing human samples and using knockout ani-
mals will be useful to answer this question and to assess whether DP8 and/or
DP9 are potential targets for the development of therapeutics in the treatment
of infertility.
As above, individual DP specific inhibition profiles have also been used to
assess the level of DP8/9 specific activity in human brain, rats and mice.
Stremenova et al. identified DP8/9 as the major enzymes contributing to
detectable DP activity in non-malignant human brain tissue.
132
DP8/9 have
also been identified as major enzymes contributing to DP activity in rat
brains, with comparisons made between crude brain extracts isolated from
wild-type and DP4 deficient rats.
133
Using DP selective inhibitors, Freker et
al. found that in brain, the level of DP8/9 activity was higher than that of DP4
and lower than the activity attributable to the related DP2.
133
In a similar
study using DP4 wild type and DP4
-/-
mice, DP8/9 were identified as strong
contenders for the observed DP activity in murine brain.
134
In addition, this
Ansorge et al. study identified both DP8 and DP9 as the most probable
enzymes responsible for the remaining observed DP4-like activity in skin and
hearttissueofDP4
-/-
mice.
134
DP8 and DP9 mRNA is detected at high levels
in both these tissues as previously discussed. Yu et al. performed a similar
study with their focus being on determining the in vivo expression and dis-
tribution of both DP8 and DP9 in human baboon and mouse tissues.
131
This
study found that both DP8/9 significantly contribute to the levels of DP
activity observed in peripheral blood mononucleocytes (PBMCs), the thymus,
spleen, colon, lung, liver brain, muscle, testis, pancreas, adipose and adrenal
tissues.
131
Both DP8/9 have been implicated in regulating the immune response. Initial
reverse-transcriptase polymerase chain reaction (RT-PCR) suggested that full-
length DP8 expression was upregulated in activated T cells.
6
DP8/9 specific
activity has since been detected in human peripheral blood leukocytes (lym-
phocytes and monocytes), Jurkat, and U937 (a human monocytic cell line)
cells
135
DP8/9 activity levels were similar in all leukocyte cell types tested
135
suggesting that DP8/9 have ubiquitous level of activity within the immune
system. Increasing evidence has been mounting for the involvement of DP9/9 in
regulating the immune response
134
, thus making them potential targets for the
development of anti-inflammatory based therapeutics which will be discussed
later in this chapter.
1.4.2.1 Non-Enzymatic Roles of DP8 and DP9:
Protein-Binding Partners
Potential roles for DP8 and DP9 in apoptosis, wound healing, and migration
have been investigated.
136,137
Using 293T cells, transient transfections were
