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: EC:3.4.22.56 (
caspase-3
)
35,750
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Cytotoxic effects of cisplatin occur primarily through apoptosis. Though several pro- and anti-apoptotic signaling molecules have been identified to play an important role in mediating the ototoxic, nephrotoxic, and neurotoxic side-effects of cisplatin, the underlying mechanism is yet to be fully characterized. We reported that nitration of
LIM domain only 4
(
LMO4
), a transcriptional regulator, facilitates cochlear apoptosis in cisplatin-induced ototoxicity. However, its role in cisplatin-mediated nephrotoxicity and neurotoxicity is poorly understood. Therefore, HK2, and SH-SY5Y cells were employed along with UBOC1 cells, to investigate the perturbations of
LMO4
in cisplatin-induced cytotoxicity, in renal, neuronal, and auditory cells, respectively. Cisplatin induced an increase in the expression of active
caspase-3
, indicating cellular apoptosis, and increased the nitration of proteins, 24 h post-treatment. Immunostaining with anti-nitrotyrosine and anti-
LMO4
indicated that nitrotyrosine co-localized with LMO4 protein in cisplatin treated cells. Immunoblotting with anti-
LMO4
indicated that cisplatin induced a decrease in LMO4 protein levels. However, a corresponding decrease in
LMO4
gene levels was not observed. Inhibition of protein nitration with SRI110, a peroxynitrite decomposition catalyst, attenuated cisplatin-induced downregulation of
LMO4
. More importantly, overexpression of
LMO4
mitigated the cytotoxic effects of cisplatin in UBOC1 cells while a dose-dependent decrease in LMO4 protein strongly correlated with cell viability in UBOC1, HK2, and SH-SY5Y cells. Collectively, these findings suggested a potential role of
LMO4
in facilitating the cytotoxic effects of cisplatin in auditory, renal, and neuronal cells.
...
PMID:Cisplatin-induced apoptosis in auditory, renal, and neuronal cells is associated with nitration and downregulation of LMO4. 2692 55
