BAG3 Attenuates Ischemia-Induced Skeletal Muscle Necroptosis in Diabetic Experimental Peripheral Artery Disease.

Peripheral artery disease (PAD) is characterized by impaired blood flow to the lower extremities, resulting in ischemic limb injuries. Individuals with diabetes and PAD typically have more severe ischemic limb injuries and limb amputations, but the mechanisms involved are poorly understood. Previously, we identified BAG3 as a gene within a mouse genetic locus termed limb salvage QTL1 on mouse chromosome 7 that determined the extent of limb necrosis following ischemic injury in C57Bl/6 mice.

MicroRNA regulation of BAG3.

B-cell lymphoma 2 (Bcl-2)-associated athanogene 3 (BAG3) protein is a member of BAG family of co-chaperones that modulates major biological processes, including apoptosis, autophagy, and development to promote cellular adaptive responses to stress stimuli. Although BAG3 is constitutively expressed in several cell types, its expression is also inducible and is regulated by microRNAs (miRNAs). miRNAs are small non-coding RNAs that mostly bind to the 3'-UTR (untranslated region) of mRNAs to inhibit their translation or to promote their degradation.

Mitochondrial Oxidative Phosphorylation Function and Mitophagy in Ischaemic/Reperfused Hearts from Control and High-Fat Diet Rats: Effects of Long-Term Melatonin Treatment.

Purpose: Oxidative stress causes mitochondrial dysfunction in myocardial ischaemia/reperfusion (I/R) as well as in obesity. Mitochondrial depolarization triggers mitophagy to degrade damaged mitochondria, a process important for quality control. The aims of this study were to evaluate (i) the effect of I/R on mitochondrial oxidative phosphorylation and its temporal relationship with mitophagy in hearts from obese rats and their age-matched controls, and (ii) the role of oxidative stress in these processes using melatonin, a free radical scavenger.

Mitochondrial oxidative phosphorylation and mitophagy in myocardial ischaemia/reperfusion: effects of chloroquine.

Aim: The aim of this study was to evaluate the temporal relationship between mitochondrial oxidative phosphorylation and mitophagy in rat hearts subjected to ischaemia/reperfusion. Measurements were made at specific points during the experimental protocol (snapshot approach) and by assessments of mitophagic flux, using chloroquine pre-treatment.

Methods: Isolated working rat hearts were subjected to 25 or 30 minutes of global ischaemia/10 minutes of reperfusion.

In experimental peripheral arterial disease, type 2 diabetes alters post-ischemic gene expression.

Peripheral arterial disease is characterized by impaired blood flow to tissues outside the heart due to atherosclerosis and it most frequently occurs in the lower extremities. Type 2 diabetes (T2D) is a well-known risk factor that accelerate the course and contributes to poor clinical outcomes of PAD. While there is some evidence that T2D is associated with altered expression of genes involved in regulating PAD severity, our knowledge about the specific genes and pathways involved remains incomplete.

Revisiting the Cardiotoxic Effect of Chloroquine.

Purpose: Cardiotoxicity is a well-known side effect of chloroquine. Several studies have proposed chloroquine as a potential anti-diabetic treatment but do not address this problem. The current study investigated the effect of ex vivo chloroquine treatment on (1) heart function and glucose uptake, (2) mitochondrial function and (3) in vivo treatment on heart function.