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)

Apoptosis has been implicated in the regulation of denervation-induced muscle atrophy. However, the activation of apoptotic signal transduction during muscle denervation has not been fully elucidated. The present study examined the apoptotic responses to denervation in rat gastrocnemius muscle. Following 14 days of denervation, the extent of apoptotic DNA fragmentation as determined by a cytosolic nucleosome ELISA was increased by 100% in the gastrocnemius muscle. RT-PCR and immunoblot analyses indicated that Bax was dramatically upregulated while Bcl-2 was modestly increased; however, the Bax/Bcl-2 ratio was significantly increased in denervated muscles relative to control muscles. Analyses of ELISA and immunoblots from mitochondria-free cytosol extracts showed a significant increase in mitochondria-associated apoptotic factors, including cytochrome c, Smac/DIABLO and apoptosis-inducing factor (AIF). In addition to the upregulation of caspase-3 and -9 mRNA, pro-/cleaved caspase protein and proteolytic activity levels, the X-linked inhibitor of apoptosis (XIAP) protein level was downregulated. The cleaved product of poly(ADP-ribose) polymerase (PARP) was detected in muscle samples following denervation. Although we did not find a difference in the inhibitor of DNA binding/differentiation-2 (Id2) and c-Myc protein contents between the denervated and control muscles, the protein content of tumour suppressor p53 was significantly increased in both the nuclear and the cytosolic fractions with denervation. Moreover, denervation increased the protein content of HSP70, whereas the MnSOD (a mitochondrial isoform of superoxide dismutase) protein content was diminished, which indicated that denervation might have induced cellular and/or oxidative stress. Our data show that mitochondria-associated apoptotic signalling is upregulated during muscle denervation. We interpret these findings to indicate that apoptosis has a physiologically important role in regulating denervation-induced muscle atrophy.
 ...
PMID:Mitochondria-associated apoptotic signalling in denervated rat skeletal muscle. 1577 33

Apoptosis arises from neuronal damage following an ischemic insult. Apoptosis-inducing factor (AIF) is a protein released from mitochondria in response to pro-apoptotic signals which then translocates to the nucleus and triggers DNA fragmentation. In parallel with this, pro-apoptotic signals cause the release of cytochrome c from mitochondria, activating caspase-dependent apoptosis. During post-ischemic reperfusion, reactive oxygen species (ROS) are formed in excess in mitochondria and can play a role in initiating apoptosis. In cultures, ROS are formed during post oxygen glucose deprivation (OGD) normoxia/normoglycemia that is used as a model for ischemia. In this study, we delivered viral vectors to overexpress antioxidants (GPX, catalase, CuZnSOD, or MnSOD) in mixed cortical cultures, in order to investigate the effects of ROS-reduction on the release of cytochrome c and AIF. Overexpression of MnSOD, CuZnSOD, catalase or GPX all prevented AIF translocation from mitochondria to the nucleus. Potentially, this could reflect broadly non-specific protection due to reducing ROS load. Arguing against this, overexpression of the same antioxidants did not inhibit cytochrome c release. These findings suggest a specific interaction between ROS formation and the caspase-independent route of apoptosis.
 ...
PMID:Effects of overexpression of antioxidants on the release of cytochrome c and apoptosis-inducing factor in the model of ischemia. 1942 31

Exposure of cells to mild temperatures (40 degrees C) induces thermotolerance, which renders cells resistant to subsequent toxic insults. Thermotolerance is usually associated with accumulation of heat shock proteins. This study determines whether mild thermotolerance (40 degrees C, 3h) can induce other defense proteins (e.g. antioxidants, anti-apoptosis proteins), and protect HeLa cells against apoptosis triggered by H(2)O(2). Protein expression and enzymatic activity of MnSOD and catalase were increased in thermotolerant cells, as well as intracellular glutathione levels and gamma-glutamylcysteine synthetase expression. Furthermore, levels of reactive oxygen species (ROS) were increased in thermotolerant cells, which caused mitochondrial membrane hyperpolarisation. Mild thermotolerance inhibited activation of the mitochondrial cascade of apoptosis by H(2)O(2). This entailed inhibition of mitochondrial Bax translocation, mitochondrial membrane depolarisation, cytochrome c release, activation of caspases-9/-3 and chromatin condensation. Thermotolerance inhibited H(2)O(2)-induced caspase-independent apoptosis involving apoptosis-inducing factor, and activation of p53 and increased expression of its target protein PUMA. Thermotolerance induced at mild physiological temperatures protects cells against both caspase-dependent and caspase-independent apoptosis triggered by oxidative stress.
 ...
PMID:Mild thermotolerance induced at 40 degrees C increases antioxidants and protects HeLa cells against mitochondrial apoptosis induced by hydrogen peroxide: Role of p53. 2001 68