Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04179 (MnSOD)
 2,777 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

CuZnSOD and MnSOD have been shown to exert tumour suppressive activities; however, their exact molecular mechanism is still unclear. We investigated the molecular mechanism underlying the tumour suppressive activities of CuZnSOD and MnSOD using multicellular tumour spheroid (MTS), an in vitro tumour model. Overexpression of CuZnSOD and MnSOD significantly suppressed the growth of A549 and MCF-7 MTS, supporting a critical role(s) of reactive oxygen species (ROS) in tumour growth. In solid tumours, ROS is produced by metabolic stress due to insufficient oxygen and glucose supply and induces necrosis that is known to promote tumour progression by releasing the proinflammatory cytokine HMGB1. We observed that CuZnSOD and MnSOD overexpression prevents metabolic stress-induced necrosis and HMGB1 release by inhibiting mitochondrial ROS and intracellular O2- production in response to glucose depletion in two dimensional cell culture. CuZnSOD and MnSOD overexpression also significantly repressed the occurrence of necrosis that was observed during MTS culture. In human tumour tissues including lung pulmonary adenocarcinoma, CuZnSOD and MnSOD expression was detected in the para-necrotic region that was identified by the expression of a hypoxic marker carbonic anhydrase (CA) IX. These results suggest that CuZnSOD and MnSOD may suppress tumour growth through inhibiting metabolic stress-induced necrosis and HMGB1 release via inhibiting metabolic stress-induced mitochondrial ROS production.
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PMID:CuZnSOD and MnSOD inhibit metabolic stress-induced necrosis and multicellular tumour spheroid growth. 2051 11

Acetaminophen (APAP) hepatotoxicity remains the leading cause of drug-induced liver injury due to the lack of safe and effective therapeutic agents. Berberine (BBR) is a natural alkaloid derived from traditional medicine Rhizoma Coptidis and possesses various pharmacological properties. The aim of this study was to explore the hepatoprotective effects and underlying mechanisms of BBR on APAP-induced hepatotoxicity. Our results indicated that BBR pretreatment significantly ameliorated APAP-induced hepatic pathological abnormalities and attenuated the elevations of serum aminotransferases and liver/body weight ratio. Compared to APAP group, BBR notably increased the levels of hepatic UDP-glucuronosyltransferases and sulfotransferases, whereas failed to ameliorate APAP-induced GSH depletion. Pretreatment with BBR significantly reduced hepatic MDA and MPO levels, inhibited JNK phosphorylation and up-regulated the expression of nuclear Nrf-2 and its downstream gene Mn-SOD. Additionally, BBR obviously prevented APAP-induced DNA fragmentation. Furthermore, BBR pretreatment dramatically reduced the expression of pro-inflammatory cytokines, HMGB1, p-p65 and cleaved caspase-1 and inhibited the infiltration of macrophages and neutrophils. Taken these results together, BBR exhibits notable preventive effects on APAP-induced hepatotoxicity by inhibiting oxidative stress, hepatocyte necrosis and inflammatory response.
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PMID:Hepatoprotective effects of berberine on acetaminophen-induced hepatotoxicity in mice. 2986 14