Pb2+ exposure alters the lens alpha A-crystallin protein profile in vivo and induces cataract formation in lens organ culture.
Epidemiological data supports lead exposure as a risk factor for cataract development. Previous studies which demonstrated oxidative imbalances in the lens following in vivo Pb(2+) exposure support the idea that lead exposure can alter the lens biochemical homeostasis which may ultimately lead to loss of lens clarity with time. alpha-Crystallin, a major lens structural protein and molecular chaperone, undergoes various post-translational modifications upon aging which may contribute to decreased chaperone function and contribute to loss of lens clarity. This study evaluated the impact of 5 weeks of oral Pb(2+) exposure (peripheral Pb(2+) level approximately 30 microg/dL) on the alphaA-crystallin protein profile of the lens from Fisher 344 rats. Decreases in relative protein spot intensity of more acidic forms of alphaA- and betaA(4)-crystallin and of truncated forms of alphaA-crystallin were noted. This data indicates that changes in post-translational processing of crystallins do occur in vivo following short courses of clinically relevant Pb(2+)-exposure. In addition, organ culture of lenses from 4.5-month-old rats in 5 microM Pb(2+) resulted in opacities, demonstrating that lead is toxic to the lens and can induce a loss of lens clarity.
Neal
R
R
Laboratory of Mechanisms of Ocular Disease, National Institutes of Health, National Eye Institute, Protein Biochemistry Section, NIH Campus Building 7, Bethesda, MD 20892, USA. nealr@nei.nih.gov
Aykin-Burns
N
N
Ercal
N
N
Zigler
J S
JS
D000818:Animals; D002386:Cataract / Q000139:chemically induced* / Q000235:genetics* / Q000378:metabolism; D007908:Lens, Crystalline / Q000187:drug effects* / Q000378:metabolism; D009924:Organ Culture Techniques; D009942:Organometallic Compounds / Q000633:toxicity*; D040081:Protein Array Analysis / Q000379:methods*; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D038202:alpha-Crystallin A Chain / Q000096:biosynthesis / Q000235:genetics*
D009942:Organometallic Compounds; D038202:alpha-Crystallin A Chain; C008261:lead acetate