Changes in Na-K ATPase and protein kinase C activities in peripheral nerve of acrylamide-treated rats.
In previous studies on rat peripheral nerve, we showed that acrylamide (ACR) exposure was associated with alterations in axonal and Schwann cell elemental composition that were consistent with decreased Na-K ATPase activity. In the present corollary study, the effects of ACR exposure on Na-K ATPase activity were determined in sciatic and tibial nerves. Subacute ACR treatment (50 mg/kg/d x 10 d, ip) significantly (p < .05) decreased Na-K ATPase activity by 45% in sciatic nerve but did not affect this activity in tibial nerve. Subchronic ACR treatment (2.8 mM in drinking water for 30 d) significantly decreased (p < .05) Na-K ATPase activities by 19% and 35% in sciatic and tibial nerves, respectively. Na-K ATPase activity was not altered in sciatic nerve homogenates exposed to 1.0 mM ACR in vitro. Since protein kinase C (PKC) has been proposed to play a role in the modulation of membrane Na-K ATPase function, PKC activity was also measured in sciatic nerve homogenates and subcellular fractions prepared from control and ACR-treated rats. Regardless of the ACR treatment protocol, PKC activity was elevated in nerve cytosol, but not in a particulate fraction. The results of this study suggest that decreased Na-K ATPase activity is involved in ACR-induced perturbation of axoplasmic and Schwann cell elemental composition in rat peripheral nerves and that loss of activity is not due to direct chemical inhibition of the enzyme. The role of PKC in ACR neurotoxicity requires further elucidation.
Lehning
E J
EJ
Department of Anesthesiology, School of Medicine, S.U.N.Y. Stony Brook 11794-8480.
LoPachin
R M
RM
Mathew
J
J
Eichberg
J
J
D020106:Acrylamide; D000178:Acrylamides / Q000008:administration & dosage / Q000633:toxicity*; D000704:Analysis of Variance; D000818:Animals; D001681:Biological Assay; D008297:Male; D010525:Peripheral Nerves / Q000187:drug effects* / Q000201:enzymology*; D011493:Protein Kinase C / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000187:drug effects / Q000201:enzymology; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*; D013979:Tibial Nerve / Q000187:drug effects / Q000201:enzymology
D000178:Acrylamides; D020106:Acrylamide; D011493:Protein Kinase C; D000254:Sodium-Potassium-Exchanging ATPase