The improvement effect of L-Lys as a chemical chaperone on STZ-induced diabetic rats, protein structure and function.
BACKGROUND
L-Lysine (L-Lys) has been known as an inhibitor of protein glycation; however, its long-term use for diabetes treatment considering different aspects of diabetic complication is not seen in the literature. In addition, the effect of L-Lys, as a chemical chaperone, was considered on protein folding and activity.


METHODS
The streptozotocin-induced diabetic rats were used as a model of diabetes. Normal and diabetic rats were studied for 5 months with and without 0.1% of L-Lys in drinking water. Serum glucose, advanced glycation end product (AGEs), haemoglobin A(1C) (HbA(1c)), triglyceride, total cholesterol, HDL-cholesterol, antioxidant activity, advanced oxidation protein products, fasting insulin level and body weight were determined at 4-week intervals. Heat shock protein (HSP)70, Lecithin: cholesterol acyl transferase (LCAT) and paraoxonase activity were determined 1 week after diabetes induction (time 0), and after 3 and 5 months. The structure of glycated and normal serum albumin (Alb) in the presence and absence of L-Lys was also investigated in an in vitro study using spectrofluorometry and circular dichroism (CD).


RESULTS
We found that L-Lysine therapy prevented diabetic- induced increases in Glc, AGE, HbA(1c), triglyceride, total- and LDL- cholesterol, and it caused an increase in the decreased antioxidant capacity, HDL-c, HDL functionality and HSP70. L-Lys had no effect on serum insulin level. The conformation of Alb changed due to glycation and L-Lys retained it similar to the native.


CONCLUSIONS
L-Lys, not only as an inhibitor of glycation but also as a chemical chaperone and a protein chaperone inducer, causes effective changes in many parameters of the model animals. However, it is not enough to achieve complete improvement.
Jafarnejad
A
A
Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Bathaie
S Z
SZ
Nakhjavani
M
M
Hassan
M Z
MZ
Banasadegh
S
S
D000818:Animals; D043303:Aryldialkylphosphatase / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D001798:Blood Proteins / Q000737:chemistry* / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy*; D006442:Glycated Hemoglobin / Q000032:analysis; D017127:Glycation End Products, Advanced / Q000097:blood; D018840:HSP70 Heat-Shock Proteins / Q000097:blood; D008055:Lipids / Q000097:blood; D008239:Lysine / Q000627:therapeutic use*; D008297:Male; D007862:Phosphatidylcholine-Sterol O-Acyltransferase; D011487:Protein Conformation; D051381:Rats; D017208:Rats, Wistar; D012709:Serum Albumin / Q000032:analysis / Q000737:chemistry; D000093423:Glycated Serum Albumin
D043303:Aryldialkylphosphatase; D001786:Blood Glucose; D001798:Blood Proteins; D006442:Glycated Hemoglobin; D017127:Glycation End Products, Advanced; D018840:HSP70 Heat-Shock Proteins; D008055:Lipids; D008239:Lysine; D007862:Phosphatidylcholine-Sterol O-Acyltransferase; D012709:Serum Albumin; D000093423:Glycated Serum Albumin