Tumor necrosis factor alpha stimulates p62 accumulation and enhances proteasome activity independently of ROS.

Circulating TNF-α levels are elevated in a wide variety of cardiovascular pathologies including congestive heart failure (CHF). This cytokine is one of the leading mediators of the immune inflammatory response with widespread biological functions regulated by membrane receptors. The pathophysiological implication of the downstream effects of activating the TNF-α system in CHF appears to depend on its direct effects on the heart and endothelium.

Doxorubicin induces protein ubiquitination and inhibits proteasome activity during cardiotoxicity.

Anthracycline-induced cardiotoxicity is a clinically complex syndrome that leads to substantial morbidity and mortality for cancer survivors. Despite several years of research, the underlying molecular mechanisms remain largely undefined and thus effective therapies to manage this condition are currently non-existent. This study therefore aimed to determine the contribution of the ubiquitin-proteasome pathway (UPP) and endoplasmic reticulum (ER)-stress within this context.

Autophagy upregulation promotes survival and attenuates doxorubicin-induced cardiotoxicity.

This study evaluated whether the manipulation of autophagy could attenuate the cardiotoxic effects of doxorubicin (DXR) in vitro as well as in a tumour-bearing mouse model of acute doxorubicin-induced cardiotoxicity. We examined the effect of an increase or inhibition of autophagy in combination with DXR on apoptosis, reactive oxygen species (ROS) production and mitochondrial function. H9C2 rat cardiac myoblasts were pre-treated with bafilomycin A1 (autophagy inhibitor, 10 nM) or rapamycin (autophagy inducer, 50 μM) followed by DXR treatment (3 μM).

Daunorubicin therapy is associated with upregulation of E3 ubiquitin ligases in the heart.

Daunorubicin (DNR) and doxorubicin (DOX) are two of the most effective anthracycline drugs known for the treatment of systemic neoplasms and solid tumors. However, their clinical use is hampered due to profound cardiotoxicity. The mechanism by which DNR injures the heart remains to be fully elucidated.

Tumor necrosis factor alpha (TNF-α) inactivates the PI3-kinase/PKB pathway and induces atrophy and apoptosis in L6 myotubes.

Muscle atrophy poses a serious concern to patients inflicted with inflammatory diseases. An increasing body of evidence implies that TNF-α plays a critical role in muscle atrophy in a number of these clinical settings. The mechanisms mediating its effects are not completely understood and conflicting data regarding its anabolic and catabolic actions exists.