Page 17 - SFRBMdot July 2015

Literature Review

ImpL2 protein is involved in chronic wasting of cancer patients’ tissues
needed for its proliferation (Reviewed by Ines Batinic-Haberle, Duke

University School of Medicine).
Malignant Drosophila Tumors Interrupt Insulin Signaling to Induce

Cachexia-like wasting. Figueroa-Clarevega A and Bilder D, Dev Cell 33,

47-55, 2015.

Systemic Organ Wasting Induced by Localized Expression of the
Caffeic acid attenuates rat liver reperfusion injury through Sirt3-
Secreted Insulin/IGF Antagonist ImpL2. Kwon Y, Song W, Droujinine I,
dependent regulation of mitochondrial respiratory chain. Mu H, Li Q,
Hu Y, Asara JM, Perrimon N, Dev Cell 33, 36-46, 2015.
Pan C, Liu Y, Yan L, Hu B, Sun K, Chang X, Zhao X, Fan J, Han J. Free

Pro-inlammatory cytokines TNF-α, IL-1 and IL-6 were previously Radic Biol Med. 2015 May 7. pii: S0891-5849(15)00196-3. doi: 10.1016/j.

implicated to be involved in wasting under different conditions. Here freeradbiomed.2015.04.033.

the researchers led by David Bilder of University of California, Berkley
Caffeic acid (CA) is a well-known antioxidant. Yet its mechanism of
and Norbert Perrimon from Harward Medical School explored another
action, in particular, in preventing ischemic injury has remained elusive.
underlying mechanism in organ wasting. Organ wasting has been seen
Using rat liver ischemia/reperfusion injury as a model, Mu et al have

in 80% of cancer patients, contributing to the 20% of deaths. The recent
shown that CA protection of liver ischemic injury is mediated by sirtuins
appreciation of parallels in physiological regulations between lies and
3 (sirt3), a mitochondrial deacetylase that is known to be involved in
humans makes Drosophila an excellent model to gain insight into genetic
cell stress response and metabolic boosting. The authors found that
factors driving human cancers. In a Drosophila model of organ wasting, the
after ischemic reperfusion, levels of sirt3 and activities of mitochondrial
over-proliferation of intestinal stem cells was induced by Yorkie, the Yap1
respiration were decreased. Further studies found that mitochondrial
oncogene ortholog. The transcription coactivator yorkie (yki) regulates
complex I subunit 9 and complex II subunit A underwent increased
growth, repair and regeneration of a transcriptional program required
acetylation due to a down-regulation of sirt3. Interestingly, when CA was
for cell proliferation and survival. The authors show that induction of
administered during the process of ischemic reperfusion, level of sirt3
insulin/IGF antagonist, ImpL2, speciically by overproliferating gut, is at
and activities of mitochondrial respiration could be partially restored

least one of the major contributors to organ wasting. Induction of ImpL2 while level of oxidative stress was attenuated, demonstrating that CA’s

in overproliferating gut is associated with a reduction in a systemic
antioxidant activity is mediated by sirt3 and this mediation was likely
insulin growth factor, IGF, signaling. Downregulation of IGF signaling
due to CA’s binding to sirt3. Although the sites of acetylation in this study
in skeletal muscles decreases Akt activity and in turn increases Foxo
was not determined, the study indeed provides convincing evidence
activity which induces muscles protein degradation through ubiquitin-
that CA can prevent liver ischemic injury and this prevention is due to
proteosome system and autophagy (Han HQ et al Int J Biochem Cell Biol
its binding to sirt3. Such binding may stabilize sirt3 and also enhance
2013). Stimulation of TGF-α family members, myostatin/activing and in
its deacetylation activity, leading to removal of acetyl groups from key
turn Smad2/3 is involved in catabolism of muscle proteins also (Fearon
mitochondrial proteins to counteract the damaging effects of ischemic
K et al Cell Metab 2012, Han HQ et al 2013). However, disparity in gene
reperfusion injury. This mechanism should also be expected to operate

expression of glycolytic enzymes and activity of insulin/IGF signaling in other organs under the condition of ischemic injury (Reviewed by

between gut and other tissues is seen. The expression of glycolityc
Liang-Jun Yan, University of North Texas Health Science Center).
enzymes and central component of IGF pathway were upregulated in

gut as the rapid synthesis of macromolecules via aerobic glycolysis is

SFRBM Newsletter // July 2015 // Literature Review

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