Recombinant human islet amyloid polypeptide forms shorter fibrils and mediates β -cell apoptosis via generation of oxidative stress.

Recombinant human islet amyloid polypeptide forms shorter fibrils and mediates β -cell apoptosis via generation of oxidative stress. Biochem J. 2017 Oct 18;: Authors: Dubey R, Minj P, Malik N, Sardesai DM, Kulkarni SH, Acharya JD, Bhavesh NS, Sharma S, Kumar A Abstract Protein aggregation play an important role in many human diseases including Alzheimer's, Parkinson's and Type 2 diabetes mellitus (T2DM). Human islet amyloid polypeptide (hIAPP) forms amyloid plaques in pancreas of T2DM subjects that are involved in deteriorating islet function and in mediating β- cell apoptosis. However, the detailed mechanism of action, structure and nature of toxic hIAPP species responsible for this effect remains elusive till date mainly due to the high cost associated with the chemical synthesis of pure peptide required for these studies. We attempted to obtain structural and mechanistic insights into the hIAPP aggregation process using recombinant hIAPP (rhIAPP) isolated from Escherichia coli Results from biophysical and structural studies indicate that the rhIAPP self-assembled into highly pure, β -sheet rich amyloid fibrils with uniform morphology. rhIAPP-mediated apoptosis in INS-1E cells was associated with increased oxidative stress and changes in mitochondrial membrane potential. The transcript levels of apoptotic genes - Caspase-3 and Bax were found to be up-regulated while the levels of the anti-apoptotic gene - Bcl2 was down-regulated...
Source: The Biochemical Journal - Category: Biochemistry Authors: Tags: Biochem J Source Type: research