As the strong Zn2+ exposures initially employed are of uncertain direct physiological relevance, we next examined effects of the sulfhydryl-oxidizing agent DTDP, which impairs Zn2+ binding to cytosolic Zn2+ buffering proteins, and thus reproduces deficiencies in cytosolic Zn2+ buffering likely caused by oxidative stress and acidosis during in vivo cerebral ischemia. The gene discussed is PROS1; the disease is brain ischemia.