Dual actions of lindane (γ-hexachlorocyclohexane) on calcium homeostasis and exocytosis in rat PC12 cells.

The persistent organochlorine pesticide lindane is still abundantly found in the environment and in human and animal tissue samples. Lindane induces a wide range of adverse health effects, which are at least partially mediated via the known inhibition of GABA(A) and glycine receptors. Additionally, lindane has been reported to increase the basal intracellular Ca(2+) concentration ([Ca(2+)](i)). As Ca(2+) triggers many cellular processes, including cell death and vesicular neurotransmitter release (exocytosis), we investigated whether lindane affects exocytosis, Ca(2+) homeostasis, production of reactive oxygen species (ROS) and cytotoxicity in neuroendocrine PC12 cells. Amperometric recordings and [Ca(2+)](i) imaging experiments with fura-2 demonstrated that lindane (≥ 10 µM) rapidly increases basal exocytosis and basal [Ca(2+)](i). Additional imaging and electrophysiological recordings revealed that this increase was largely due to a lindane-induced membrane depolarization and subsequent opening of N- and P/Q-type voltage-gated Ca(2+) channels (VGCC). On the other hand, lindane (≥ 3 µM) induced a concentration-dependent but non-specific inhibition of VGCCs, thereby limiting the lindane-induced increase in basal [Ca(2+)](i) and exocytosis. Importantly, the non-specific inhibition of VGCCs also reduced stimulation-evoked exocytosis and Ca(2+) influx. Though lindane exposure concentration-dependently increased ROS production, cell viability was not affected indicating that the used concentrations were not acute cytotoxic. These combined findings indicate that lindane has two, partly counteracting effects. Lindane causes membrane depolarization, thereby increasing basal [Ca(2+)](i) and exocytosis. In parallel, lindane inhibits VGCCs, thereby limiting the basal effects and reducing stimulation-evoked [Ca(2+)](i) and exocytosis. This study further underlines the need to consider presynaptic, non-receptor-mediated effects in human risk assessment.

Microbial production of bulk chemicals: development of anaerobic processes.

Innovative fermentation processes are necessary for the cost-effective production of bulk chemicals from renewable resources. Current microbial processes are either anaerobic processes, with high yield and productivity, or less-efficient aerobic processes. Oxygen utilization plays an important role in energy generation and redox metabolism that is necessary for product formation. The aerobic productivity, however, is relatively low because of rate-limiting volumetric oxygen transfer; whereas the product yield in the presence of oxygen is generally low because part of the substrate is completely oxidized to CO2. Hence, new microbial conversion processes for the production of bulk chemicals should be anaerobic. In this opinion article, we describe different scenarios for the development of highly efficient microbial conversion processes for the anaerobic production of bulk chemicals.