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August 17-18, 2017 | Toronto, Canada
ANNUAL BIOTECHNOLOGY CONGRESS
Ann Biol Sci, 2017
ISSN: 2348-1927
Hedgehog signaling scenario in the hematopoietic microenvironment of chronic agricultural pesticide
induced aplastic bone marrow
Sujata Law
Calcutta School of Tropical Medicine, India
O
veractivation of hedgehog signaling has been found
to be associated with a wide variety of hematological
and nonhematological malignancies including cancer stem
cells. However, involvement of the hedgehog signaling
system in bone marrow hematopoietic microenvironment
during the progression of the bone marrow aplasia
is absolutely unknown. In the present work, we have
developed an agricultural pesticide formulation (fungicide,
organophosphate and pyrethroid) induced bone marrow
aplasia mouse model to recapitulate the human aplastic
anemia like condition in the laboratory to study the aplastic
hematopoietic microenvironment in the light of HH-GLI
signaling pathway. Our study has unfolded the fact that
chronic pesticide exposure caused downregulation of
intrasignaling feedback of PATCH1 and GLI1 by inhibiting the
SMO internalization and upregulating downstream negative
regulators SU(FU), PKC-δ and βTrCP. Upregulation of negative
regulators not only hampers the execution of the hedgehog
signaling but also cripples the autocrine-paracrine crosstalk
in between bone marrow primitive compartment and
stromal compartment. Simultaneously, individual pesticide
versus hedgehog signaling study revealed that hexaconazole
disrupted hematopoietic hedgehog signaling activation
by inhibiting SMO and facilitating PKC-δ expression.
Contrarily, chloropyriphos increased the cytoplasmic
sequestration and degradation of GLI1 by upregulating
SU(FU) and βTrCP sequentially. Whereas, cypermethrin
mediated antagonization of the hedgehog signaling was
circumvented by noncanonical activation of GLI1. However,
such marrow degenerative condition can be compensated
by the recombinant sonic hedgehog. We can conclude that
pesticide exposure induced bone marrow aplasia is the
direct manifestation of downregulated hedgehog signaling
in the bone marrow microenvironment and application of
recombinant sonic hedgehog could be a way to improve the
overall scenario.
e:
msuj2002@yahoo.co.inAnn Biol Sci, 2017, 5:3
DOI: 10.21767/2348-1927-C1-003