Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0344329 (collapse)
 28,634 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous evidence revealed significant elevated liver cancer mortality in the areas where water was contaminated with hexavalent chromium [Cr(vi)], which highlighted that we should pay more attention to Cr(vi)-induced cytotoxicity in hepatocytes. We found that Clusterin (CLU) was up-regulated in Cr(vi)-exposed L-02 hepatocytes, but the role CLU played in Cr(vi)-induced cytotoxicity has never been explored. In the present study, we demonstrate Cr(vi) targeted mitochondrial respiratory chain complex I (MRCC I) activity and induced reactive oxygen species (ROS) accumulation, which caused mitochondrial damage that was characterized by the increase of permeability transition pore (PTP) open rate, the collapse of mitochondrial membrane potential (MMP), and the release of apoptosis-inducing factor (AIF) and Cytochrome C (Cyt C) from mitochondria to cytoplasm, which then induced cell viability loss and increased aspartate transaminase (AST)/alanine transaminase (ALT) leakage. We reveal that Cr(vi) may regulate CLU expression through the ROS-ataxia telangiectasia mutant (ATM)-insulin-like growth factor 1 (IGF-1) axis, and CLU expression was positively correlated to MRCC I activity. We further confirmed that CLU may regulate MRCC I activity via modulating its subunit nicotinamide adenine dinucleotide dehydrogenase (ubiquinone) Fe-S protein 3 (NDUFS3) expression. By the establishment of CLU over-expression cells, we found that over-expression of CLU alleviated Cr(vi)-induced MRCC I inhibition and further rescued cell viability loss and reduced AST and ALT leakage. Thus, we reached the conclusion that the CLU-induced increase of MRCC I activity protected against Cr(vi)-induced cytotoxicity. The present research will provide new experimental evidence for thoroughly clarifying the cytotoxicity and the carcinogenic mechanism of Cr(vi).
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PMID:Clusterin increases mitochondrial respiratory chain complex I activity and protects against hexavalent chromium-induced cytotoxicity in L-02 hepatocytes. 3071 57

Brain is not homogenous and neurons from various brain regions are known to have different vulnerabilities to mitochondrial mutations and mitochondrial toxins. However, it is not clear if this vulnerability is connected to different energy metabolism in specific brain regions. Here, using live-cell imaging, we compared mitochondrial membrane potential and nicotinamide adenine dinucleotide (NADH) redox balance in acute rat brain slices in different brain regions and further detailed the mitochondrial metabolism in primary neurons and astrocytes from rat cortex, midbrain and cerebellum. We have found that mitochondrial membrane potential is higher in brain slices from the hippocampus and brain stem. In primary co-cultures, mitochondrial membrane potential in astrocytes was lower than in neurons, whereas in midbrain cells it was higher than in cortex and cerebellum. The rate of NADH production and mitochondrial NADH pool were highest in acute slices from midbrain and midbrain primary neurons and astrocytes. Although the level of adenosine tri phosphate (ATP) was similar among primary neurons and astrocytes from cortex, midbrain and cerebellum, the rate of ATP consumption was highest in midbrain cells that lead to faster neuronal and astrocytic collapse in response to inhibitors of ATP production. Thus, midbrain neurons and astrocytes have a higher metabolic rate and ATP consumption that makes them more vulnerable to energy deprivation.
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PMID:Variability of mitochondrial energy balance across brain regions. 3319 Feb 29


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