Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P42574 (
caspase-3
)
45,978
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
A previous study showed that
small G protein signaling modulator 3
(
SGSM3
) was highly correlated with Cx43 in heart functions and that high levels of
SGSM3
may induce Cx43 turnover through lysosomal degradation in infarcted rat hearts. Here, we investigated the protective effects of kenpaullone on cardiomyocytes following H
2
O
2
-induced oxidative stress mediated by the interaction of
SGSM3
with Cx43. We found that the gap junction protein Cx43 was significantly down-regulated in an H
2
O
2
concentration-dependent manner, whereas expression of
SGSM3
was up-regulated upon H
2
O
2
exposure in H9c2 cells. The effect of kenpaullone pretreatment on H
2
O
2
-induced cytotoxicity was evaluated in H9c2 cells. H
2
O
2
markedly increased the release of lactate dehydrogenase (LDH), while kenpaullone pretreatment suppressed LDH release in H9c2 cells. Moreover, kenpaullone pretreatment significantly reduced ROS fluorescence intensity and significantly down-regulated the level of apoptosis-activating genes (cleaved
caspase-3
, cleaved caspase-9 and cytochrome C), autophagy markers (LC3A/B), and the Cx43-interacting partner
SGSM3
. These results suggest that kenpaullone plays a role in protecting cardiomyocytes from oxidative stress and that the turnover of Cx43 through
SGSM3
-induced lysosomal degradation underlies the anti-apoptotic effect of kenpaullone.
...
PMID:Protective effects of kenpaullone on cardiomyocytes following H
2
O
2
-induced oxidative stress are attributed to inhibition of connexin 43 degradation by SGSM3. 2957
