Acute Tobacco Smoke Exposure Promotes Mitochondrial Permeability Transition in Rat Heart

Abstract

Chronic exposure to tobacco smoke is known to impair mitochondrial function. However, the effect of acute tobacco smoke exposure (ATSE) in vivo, as might occur in social settings, on mitochondrial function and calcium handling of cardiac cells has not been examined. It was hypothesized that ATSE might adversely modify mitochondrial function as reflected in mitochondrial energetics, membrane potential, and calcium transport. Mitochondria were isolated from the hearts of adult rats either exposed to 6 h of environmental tobacco smoke ( approximately 60 mg/mm3 tobacco smoke particles) or sham exposure. To model a calcium stress similar to ischemia/reperfusion, mitochondria were exposed to a Ca2+ bolus with measurement of membrane potential, energetics, Ca2+uptake and release, and redox state. ATSE mitochondria were characterized by significantly higher ADP-stimulated ATP production and a more reduced redox state (NADH ratio) under basal conditions without observed changes in resting Psim. Exposure of ATSE mitochondria to Ca2+stress resulted in significantly more rapid depolarization of Psim. The initial rate of Ca2+uptake was not altered in ATSE mitochondria, but CsA-sensitive Ca2+ release was significantly increased. ATSE does not significantly alter resting mitochondrial function. However, ATSE modifies the response of cardiac mitochondria to calcium stress, resulting in a more rapid depolarization and subsequent release of Ca2+ via the mitochondrial permeability transition (MPT).

The Role of Lipotoxicity in Smoke Cardiomyopathy

“…In actuality, apoptosis has a strict association with oxidative stress and energy metabolism. Direct damage to the cell membrane and ROS-induced DNA and mitochondrial damage are all signs of ROS-induced apoptosis [16] . The present study generated evidence for increased ROS and mitochondrial dysfunction as a potential pathway for myocyte hypertrophy and apoptosis.…”

“…Oxidative stress plays a major role in the cardiac remodeling induced by tobacco smoke. The main sources of ROS include nicotinamide adenine dinucleotide phosphate-oxidases (NADPH oxidases) and mitochondrial respiration [15] , [16] . In fact, previous studies have suggested that exposure to cigarette smoke induces NADPH oxidases [15] and affects mitochondrial respiration, increasing ROS formation [16] .…”

“…In fact, apoptosis has a strict association with oxidative stress and energy metabolism. ROS-induced cardiac apoptosis is mediated through signaling systems, including intracellular calcium signaling, direct damage to the cell membrane, lipid oxidation, DNA and mitochondrial damage and proto-oncogene activation [16] , [20] . The changes in energy metabolism leading to lipotoxicity are another important cause of apoptosis [21] , [22] , [23] .…”

Molecular and Biochemical Changes of the Cardiovascular System due to Smoking Exposure

“…Thus smoke exposure modifies the response of cardiac mitochondria to calcium stress, resulting in a more rapid depolarization and subsequent release of Ca 2+ via the mitochondrial permeability transition (MPT) [91].…”

Mitochondrial Dysfunction in Atherosclerosis

“…193 Acute tobacco smoke exposure, as might occur in social settings, increases the susceptibility of rat cardiac mitochondria to calcium and promotes mitochondrial permeability transition. 194 Second-hand smoke significantly increased aortic mtDNA damage, decreased ANT activity, and increased nitration and inactivity of SOD2 in mice. 61 Exposure to second-hand smoke in the background of hypercholesterolemia increased atherogenesis and synergistically enhanced mitochondrial damage.…”