Asbestos, Quebec: The Town, the Mineral, and the Local-Global Balance Between the Two

From the late 19th to the late 20th century, the cities and industries of the world became increasingly reliant on fireproof materials made from asbestos. As asbestos was used more and more in building materials and household appliances, its harmful effect on human health, such as asbestosis, lung cancer and mesothelioma, became apparent. The dangers surrounding the mineral led to the collapse of the industry in the 1980s. While the market demand and medical rejection of asbestos were international, they were also experienced in the mining and processing communities at the core of the global industry. In the town of Asbestos, Quebec, home of the largest chrysotile asbestos mine in the world, we can see how this process of market boom and bust shaped a fierce local cultural identity. This dissertation examines the global asbestos industry from a local perspective, showing how the people of Asbestos, Quebec had international reach through the work they did and the industry they continue to support today. This thesis explores how the boundaries between humans and the environment were blurred in Asbestos as a strong cultural identity was created through the interaction between people and the natural world. This work advances our understanding of the interdependence of the local-global relationship between resource industries and international trade networks, illustrating the ways it shapes communities and how communities shape it. Bringing bodies of land, human bodies, and the body politic of Asbestos, Quebec into the history of the global asbestos trade helps demonstrate how this local cultural identity grew to influence national policy and global debates on commodity flows, occupational health, and environmental justice

Disruption of Hexokinase II–Mitochondrial Binding Blocks Ischemic Preconditioning and Causes Rapid Cardiac Necrosis

Rationale: Isoforms I and II of the glycolytic enzyme hexokinase (HKI and HKII) are known to associate with mitochondria. It is unknown whether mitochondria-bound hexokinase is mandatory for ischemic preconditioning and normal functioning of the intact, beating heart. Objective: We hypothesized that reducing mitochondrial hexokinase would abrogate ischemic preconditioning and disrupt myocardial function. Methods and Results: Ex vivo perfused HKII+/- hearts exhibited increased cell death after ischemia and reperfusion injury compared with wild-type hearts; however, ischemic preconditioning was unaffected. To investigate acute reductions in mitochondrial HKII levels, wild-type hearts were treated with a TAT control peptide or a TAT-HK peptide that contained the binding motif of HKII to mitochondria, thereby disrupting the mitochondrial HKII association. Mitochondrial hexokinase was determined by HKI and HKII immunogold labeling and electron microscopy analysis. Low-dose (200 nmol/L) TAT-HK treatment significantly decreased mitochondrial HKII levels without affecting baseline cardiac function but dramatically increased ischemia-reperfusion injury and prevented the protective effects of ischemic preconditioning. Treatment for 15 minutes with high-dose (10 mu mol/L) TAT-HK resulted in acute mitochondrial depolarization, mitochondrial swelling, profound contractile impairment, and severe cardiac disintegration. The detrimental effects of TAT-HK treatment were mimicked by mitochondrial membrane depolarization after mild mitochondrial uncoupling that did not cause direct mitochondrial permeability transition opening. Conclusions: Acute low-dose dissociation of HKII from mitochondria in heart prevented ischemic preconditioning, whereas high-dose HKII dissociation caused cessation of cardiac contraction and tissue disruption, likely through an acute mitochondrial membrane depolarization mechanism. The results suggest that the association of HKII with mitochondria is essential for the protective effects of ischemic preconditioning and normal cardiac function through maintenance of mitochondrial potential. (Circ Res. 2011; 108:1165-1169.