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Complex Interactions Between Polyamines and Calpain‐Mediated Proteolysis in Rat Brain
Author(s) -
Najm Imad,
Vanderklish Peter,
Etebari Amir,
Lynch Gary,
Baudry Michel
Publication year - 1991
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1991.tb08273.x
Subject(s) - calpain , putrescine , calpastatin , spermidine , spermine , biochemistry , proteolysis , leupeptin , polyamine , chemistry , calcium , cadaverine , antipain , spectrin , proteases , endogeny , protease , biology , enzyme , cell , cytoskeleton , organic chemistry
Polyamine synthesis is induced by various extracellular signals, and it is widely held that this biochemical response participates in cell growth and differentiation. Certain of the triggers for synthesis in brain tissues also increase the breakdown of high‐molecular‐weight structural proteins, apparently by activating calcium‐dependent proteases (cal‐pains). The present experiments tested the possibility that calpain activity is modulated by polyamines. Spermine, spermidine, and putrescine all increased calcium‐dependent proteolysis of [ 14 C]casein by soluble fractions of rat brain. The order of potency was spermine > spermidine > putrescine, with apparent affinities of 30, 300, and 6.000 μ M , respectively. Each of the three polyamines at physiological concentrations also potentiated the calcium‐dependent breakdown of two endogenous high‐molecular‐weight structural proteins known to be substrates of calpain, in both supernatant and membrane fractions. The thiol protease inhibitor leupeptin, a known calpain inhibitor, also inhibited calcium‐dependent proteolysis in the presence and absence of polyamines. The polyamines did not increase the activity of purified calpain I or calpain II determined with either [ 14 C]casein or purified spectrin as the substrate, nor did they interfere with the inhibitory effects of calpastatin, an endogenous inhibitor of calpain. However, polyamines potentiated the stimulation of endogenous but not purified calpain activity produced by an endogenous calpain activator. These results suggest a rote for polyamines in protein degradation as well as protein synthesis.