Anti-HIV drugs and the mitochondria

AbstractSeveral drugs are currently used that can significantly prolong the course of the infection with the human immunodeficiency virus (HIV), the cause of the acquired immunodeficiency syndrome (AIDS). Among these drugs, the nucleosidic inhibitors of viral reverse transcriptase can alter mitochondrial (mt) function by inhibiting the mitochondrial DNA polymerase gamma (the enzyme responsible for the replication of mtDNA). Decreased mtDNA content provokes a diminished synthesis of respiratory chain enzymes, leading to alterations in mt function. These are in turn responsible for a variety of side effects frequently observed in HIV+ patients, that range from hyperlactatemia and lactic acidosis to lipodystrophy, a pathology characterized by accumulation of visceral fat, breast adiposity, cervical fat-pads, hyperlipidemia, insulin resistance and fat wasting in face and limbs. In this paper, data concerning the effects of different compounds on mitochondria, their role in the pathogenesis of lipodystrophy, and problems related to studies on the mt toxicity of antiviral drugs are reviewed and thoroughly discussed

Obesity risk during collective quarantine for the COVID-19 epidemic

In March 2020, when COVID-19 epidemics involved several countries, the WHO defined the infection as a pandemic. Government adopted measures to prevent the diffusion of infection; i.e. quarantine and isolation. One of the consequences of quarantine-induced stress is a change in lifestyle and eating habits leading to obesity. The present commentary briefly analyzes the effects of quarantine on obesity

Anti-drug antibody detection with label-free electrolyte-gated organic field-effect transistors

The efficacy of immunotherapy can be undermined by the development of an immune response against a drug/antibody mediated by anti-drug antibodies (ADAs) in treated patients. We present the first label-free EGOFET immunosensor that integrates a biological drug, Nivolumab (Opdivo©), as a specific recognition moiety to quantitatively and selectively detect ADAs against the drug. The limit of detection is 100 fM. This demonstration is a prelude to the detection of ADAs in a clinical setting in the treatment of different pathologies, and it also enables rapid screening of biological drugs for immunogenicity

Emerging role of Lon protease as a master regulator of mitochondrial functions

Lon protease is a nuclear-encoded, mitochondrial ATP-dependent protease highly conserved throughout the evolution, crucial for the maintenance of mitochondrial homeostasis. Lon acts as a chaperone of misfolded proteins, and is necessary for maintaining mitochondrial DNA. The impairment of these functions has a deep impact on mitochondrial functionality and morphology. An altered expression of Lon leads to a profound reprogramming of cell metabolism, with a switch from respiration to glycolysis, which is often observed in cancer cells. Mutations of Lon, which likely impair its chaperone properties, are at the basis of a genetic inherited disease named of the cerebral, ocular, dental, auricular, skeletal (CODAS) syndrome. This article is part of a Special Issue entitled 'EBEC 2016: 19th European Bioenergetics Conference, Riva del Garda, Italy, July 2-6, 2016', edited by Prof. Paolo Bernardi

TRPA1 Is Expressed in Central But Not in Peripheral Glia

TRPA1 are cation channels expressed in sensory neurons and in several other cell types. This channel is specifically activated by ally isothiocyanate (AITC), the pungent component of mustard oil, as well as by other electrophilic compounds. Although TRPA1 expression in central glia has been reported, its subcellular localization and its expression in peripheral glia have not been investigated before. In this paper we report the molecular and functional expression of TRPA1 in rat cortical astrocytes. Real-time RT-PCR identified low but significant amounts of TRPA1 mRNA in cortical astrocytes while no signal was seen in peripheral glia isolated from dorsal root ganglia (DRG) or in a glial cell line (DITNC-1). Calcium imaging showed AITC-induced signals in astro-cytes while no response in peripheral glia. AITC induced calcium signals in astrocytes in the presence and in the absence of extracellular calcium, suggesting an intracellular localization of TRPA1 channels. Whole cell electrophysiological recordings were performed in astrocytes, in peripheral glia and in DITNC-1 cells transfected with TRPA1 during AITC application. In TRPA1-transfected DITNC-1 cells typical TRPA1 currents were recorded with a reversal potential near 0 mV, consistent with the opening of a non-selective cation channel. No such currents were recorded in untransfected DITNC-1 cells, in astrocytes and in peripheral glial cells, where even high concentrations of AITC (up to 10 mM) induced no significant outward current. In astrocytes AITC transiently induced an outward rectifying current with the reversal potential near ?90 mV, consistent with K channel activation, likely activated by intracellular release of calcium. Our results suggest that TRPA1 channels are molecularly and functionally expressed in calcium-containing organelles of rat cortical astrocytes, with no expression in the plasma membrane

Interfering with ROS metabolism in cancer cells: the potential role of quercetin.

Abstract: A main feature of cancer cells, when compared to normal ones, is a persistent pro-oxidative state that leads to an intrinsic oxidative stress. Cancer cells have higher levels of reactive oxygen species (ROS) than normal cells, and ROS are, in turn, responsible for the maintenance of the cancer phenotype. Persistent ROS stress may induce adaptive stress responses, enabling cancer cells to survive with high levels of ROS and maintain cellular viability. However, excessive ROS levels render cancer cells highly susceptible to quercetin, one of the main dietary flavonoids. Quercetin depletes intracellular glutathione and increases intracellular ROS to a level that can cause cell death