Autoinhibitory Feedback Control over Photodynamic
Action
Mediha
Nur Zafer Yurt
Yusuf Cakmak
Gülsüm Tekin
Serdar Karakurt
Sundus Erbas-Cakmak
10.1021/acsomega.9b01410.s001
https://acs.figshare.com/articles/journal_contribution/Autoinhibitory_Feedback_Control_over_Photodynamic_Action/8947079
In biology, the activity
of enzymes is usually regulated by feedback
loops, which enables direct communication between enzymes and the
state of the cell. In a similar manner, with the intention to have
automated activity regulation, the therapeutic effect of a photosensitizer
(<b>BOD1</b>) is shown to be reduced through a negative feedback
loop initiated by the photosensitizer. Photodynamic action produces
cytotoxic <sup>1</sup>O<sub>2</sub> and this reactive oxygen species
reacts with ascorbate, generating H<sub>2</sub>O<sub>2</sub>. Peroxide-mediated
oxidation of the photosensitizer auxiliary group leads to the formation
of inactive <b>BOD2</b> from the parent photosensitizer. <b>BOD1</b> is shown to accumulate in mitochondria, and cell viability
is shown to decrease significantly with <b>BOD1</b> compared
to the loop end product, <b>BOD2</b>. Photoinduced enhancement
of fluorescence indicates the formation of inactive <b>BOD2</b> under cellular conditions, and enhanced fluorescence acts as a reporter
for the activity of the photosensitizer. We present the first example
of PDT autoinactivation, and such a feedback control mechanism would
enable a decrease in post-therapy side effects.
2019-07-17 18:36:57
feedback control mechanism
photosensitizer
cytotoxic 1 O 2
loop end product
PDT
Autoinhibitory Feedback Control
BOD 2
BOD 1
post-therapy side effects
H 2 O 2
reactive oxygen species