Stress proteins in oligodendrocytes: differential effects of heat shock and oxidative stress

Heat shock proteins (HSP) or stress proteins serve as biomarkers to identif y the contribution of stress situations underlying the pathogenesis of dege nerative diseases of the CNS. We have analyzed by immunoblot technique the constitutive and inducible occurance of stress proteins in cultured rat bra in oligodendrocytes subjected to heat shock or oxidative stress exerted by hydrogen peroxide, or a combination of both. The data demonstrate that olig odendrocytes constitutively express HSP32, HSP60 and the cognate form of th e HSP70 family of proteins, HSC70. After heat shock, HSP25, alphaB-crystall in and HSP70 were up-regulated, while after oxidative stress the specific i nduction of HSP32 and alphaB-crystallin was observed. HSP32 represents heme oxygenase 1 (HO-1), a small stress protein with enzymatic activity involve d in the oxidative degradation of heme which participates in iron metabolis m. The presence of the iron chelators phenanthroline or deferoxamine (DFO), which previously has been shown to protect oligodendrocytes from oxidative stress-induced onset of apoptosis, caused a marked stimulation of HSP32 wi thout affecting HSP70. This indicates that DFO possibly exerts its protecti ve role by directly influencing the antioxidant capacity of HO-1. In summar y, HSP in oligodendrocytes are differentially stimulated by heat stress and oxidative stress. Heme oxygenase-1 has been linked to inflammatory process es and oxidative stress, its specific up-regulation after oxidative stress in oligodendrocytes suggests that it is an ideal candidate to investigate t he involvement of oxidative stress in demyelinating diseases.