Distribution of catalase in rat brain: aminergic neurons as possible targets for ethanol effects

Abstract — Ethanol is metabolized at a slow but measurable rate in rodent brain Recent studies indicate that this process is mediated mainly by catalase. The spatial distribution of this enzyme in different brain structures is poorly known. To explore possible local imbalances between the production and elimination of ethanol-denved acetaldehydc. we investigated the regional and cellular distribution of catalase. histo- and immunohistochcmically. using serial cryostat sections trom male Wistar rats Compared to the strong pcroxisomal staining seen in liver, brain catalase staining was weak and was not immunologically detected with an anti-sheep bovine catalase antibody Activity was observed only in microperoxisomes. mainly in penkaryons of aminergic neurons, in the known groups ot adrcnergic. noradrenergic and serotoncrgic neurons of the brain stem. Little pcroxisomal staining was seen in other types of brain structures. This result contrasted to that of aldehyde dehydrogenase. which we previously observed to be widely distributed in brain structures, but with low activity in penkaryons of aminergic (especially catecholaminergic) neurons, as compared to chohnergic neurons. Our data indicate that catalase-mcdiatcd oxidation of ethanol to acetaldehydc takes place mainly in aminergic neurons, which seem to have a limited capacity for the subsequent removal via aldehyde dehydrogenase This suggests that locally produced acetaldehyde could mediate CNS effects of ethanol in these structures

Hormonal regulation of the zonated expression of cytochrome P-450 3A in rat liver

Most cytochrome P-450 enzymes are expressed characteristically in a zonated pattern in the liver. The factors responsible for this heterogenous expression are largely unknown. Here we report how growth hormone and tri-iodothyronine regulate the steroid-hydroxylating cytochrome P-450 (CYP) 3A forms, which are constitutively expressed mainly in the perivenous (downstream) liver region. By comparing cell lysates obtained from the periportal and perivenous acinar regions we observed that the elevated CYP3A expression observed after hypophysectomy was due mainly to a dramatic increase in the normally silent periportal region. This effect was particularly strong in females. Treatment with growth hormone re-established the perivenous expression pattern, a finding corroborated by immunohistochemical analysis of liver sections. Analysis of periportal and perivenous mRNA by reverse-transcriptase PCR demonstrated that in males the changes in CYP3A2 mRNA paralleled the changes at the protein level. In females, CYP3A2 mRNA was detected only after hypophysectomy, and the zonal protein changes seemed to be governed by changes in CYP3A1 mRNA levels. Treatment of hypophysectomized animals with tri-iodothyronine also suppressed the expression of CYP3A, both in males and females. However, this occurred almost exclusively in the periportal region. This was observed both at the protein level, as determined by immunoblotting and immunohistochemically, and at the CYP3A1 and 3A2 mRNA level. These results indicate that growth hormone and thyroid hormone regulate the expression of CYP3A genes zone-specifically by suppressing their transcription in the periportal (upstream) region of the liver