Effects of nicotine exposure on murine mandibular development.

Nicotine is known to affect cell proliferation and differentiation, two processes vital to proper development of the mandible. The mandible, the lower jaw in mammals and fish, plays a crucial role in craniofacial development. Malformation of the jaw can precipitate a plethora of complications including disrupting development of the upper jaw, the palate, and or impeding airway function. The purpose of this study was to test the hypothesis that in utero nicotine exposure alters the development of the murine mandible in a dose dependent manner. To test this hypothesis, wild type C57BL6 mice were used to produce in utero nicotine exposed litters by adding nicotine to the drinking water of pregnant dams at concentrations of 0 µg/ml (control), 50 µg/ml (low), 100 µg/ml (medium), 200 µg/ml (high) throughout pregnancy to birth of litters mimicking clinically relevant nicotine exposures. Resultant pups revealed no significant differences in body weight however, cephalometric investigation revealed several dimensions affected by nicotine exposure including mandibular ramus height, mandibular body height, and molar length. Histological investigation of molars revealed an increase in proliferation and a decrease in apoptosis with nicotine exposure. These results demonstrate the direct effects of nicotine on the developing mandible outside the context of tobacco use, indicating that nicotine use including tobacco alternatives, cessation methods, and electronic nicotine delivering products may disrupt normal growth and development of the craniofacial complex.

A possible role for protein kinase C activity but not cyclic nucleotide-dependent protein kinases in human natural killer cell lytic activity.

Recent evidence suggests that a Ca++, phospholipid, diacylglycerol-dependent protein kinase, protein kinase C, plays a role in the activation of cytotoxic T lymphocytes by target cells. In this investigation we have examined the role of protein kinase C in human NK cell-mediated cytolysis of K-562 cells. The protein kinase C inhibitor, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7) inhibited human NK cell-mediated cytolysis in a dose dependent manner. On the other hand, N-(2-guanidinoethyl)-5-isoquinolinesulfonamide (HA1004), a specific inhibitor of cyclic nucleotide dependent protein kinases had no effect on human NK cell-mediated cytolysis of K562 cells. There is little or no effect on protein synthesis or N-glycosylation activity in human NK cells by H-7. The relative inhibitory ability of the two inhibitors suggest that protein kinase C, acting synergistically with Ca++ mobilization, plays a role in the early stages of human NK cell-mediated cytolysis of K562 target cells.