Tumor necrosis factor-α and -β activate isozyme II of carbonic anhyrase by a direct mechanism of action

Tumor necrosis factor (TNF) is well-known as a serum protein family consisting in 2 proteins designed as TNF-ct called cachectin, and TNF-13 also called lymphotoxin. Recent studies have demonstrated that the levels of these proteins in serum are elevated in different types of cancer, including those digestives. Therefore, TNF is used as a tumoral marker. Our research has proved that gastric carcinoma patients serum powerfully activates carbonic anhydrase (CA) II (l.Pu~ca~v-DDW, Washington D.C., 682, 1997). The activating effect of gastric carcinoma patients serum upon this cytoplasmic isozyme could be produced by endogenous substances (possibly TNF) found in the serum of these patients and released during the carcinogenic process. AIM: In this paper we followed the effect of TNF-cc and TNF-13 on CA I and CAll in order to establish a possible connection between this enzyme and TNF. MATERIAL AND METHOD: We determined the effect of TNF-ct and 13 at concentrations between 10-1°-10-6M on purified CA I and CA II. CA activity has been assessed by stopped-flow method using a rapid enzymatic kinetic apparatus HI-TECH SF 51MX (England). TNF was supplied by Boehringer Ingelheim (Germany) and CA was purchased from SIGMA (USA).RESULTS: