INDUCTION BY PROSTAGLANDIN A(1) OF HEME OXYGENASE IN MYOBLASTIC CELLS- AN EFFECT INDEPENDENT OF EXPRESSION OF THE 70-KDA HEAT-SHOCK PROTEIN

Prostaglandins of the A type (PGA) induce the synthesis of 70 kDa heat shock proteins (hsp70) in a large variety of mammalian cells. Inducti on of hsp70 has been associated with a cytoprotective effect of PGA(1) after virus infection or thermal injury. In the present report we pro vide evidence that, in murine myoblasts, PGA(1) is not able to induce hsp70 expression, whereas it increases the synthesis of the constituti ve protein, hsc70, and dramatically induces the synthesis of a 32 kDa protein (p32). The p32 protein has been identified as haem oxygenase. PGA(1) acts at the transcriptional level by inducing haem oxygenase mR NA synthesis, and the signal for induction appears to be associated wi th decreased intracellular GSH levels. Haem oxygenase, a low-molecular -mass stress protein induced in mammalian cells by oxidant stress, is known to be part of a general inducible antioxidant defence pathway. T he fact that prostaglandin synthesis is stimulated in muscle during co ntraction and in the heart in response to ischaemia raises the possibi lity that induction of haem oxygenase by PGA in myoblasts could be par t of a protective mechanism in operation during stress and hypoxia.