Heme Deficiency Is Associated with Senescence and Causes Suppression of N-Methyl-d-aspartate Receptor Subunits Expression in Primary Cortical Neurons

摘要: Heme is a crucial component of many pharmacological and toxicological processes, studies have suggested that heme deficiency may play role in cellular ageing. A model ageing neurons was established using prolonged cultures BALB/c mouse primary cortical neurons. Aged displayed senescent phenotype marked up-regulation cathepsin-L expression. Down-regulation the candidate neuron-specific genes for N-methyl-D-aspartate (NMDA) receptor subunits (NMDAzeta1 -epsilon2) neurofilament light peptide (NF-L) were found to be characteristic aging process as reported vivo (Brain Res 907:71-83, 2001; Brain Mol 99:40-45, 2002). In contrast, controlling enzymes synthesis degradation (5-aminolevulinate synthase 1 oxygenase 1, respectively) up-regulated, implying depletion regulatory pool. Inhibition (by 70-80%) at different enzymic steps by succinyl acetone N-methylprotoporphyrin IX resulted earlier lowered expression NMDAzeta1 -epsilon2 NF-L. Exogenous hemin added heme-depleted cells rescued these genes. Culture from Fech(m1Pas) mutant mice demonstrating depressed showed premature senescence reduced NF-L compared with wild-type cells. Our findings suggest availability associated significant effects on synaptic function.