Induction of antioxidant enzymes by curcumin and its analogues in human islets: implications in transplantation.
OBJECTIVE
The survival of transplanted human islets is hampered by the quality of islets, which is affected by oxidative stress during isolation. The objective of this study was to determine if curcumin and its analogues could induce antioxidant enzymes in beta cells of human islets.


METHODS
The expression of antioxidant enzymes in isolated human islets exposed to curcuminoids was determined at the messenger RNA levels by real-time quantitative reverse transcription-polymerase chain reaction using Taqman probes and at the protein level by Western blot analysis. Double immunofluorescent staining of islets was carried out to determine the induction of antioxidant enzymes in beta cells.


RESULTS
Curcuminoids induced the expression of heme oxygenase 1; modulatory subunit of gamma-glutamyl-cysteine ligase; and NAD(P)H:quinone oxidoreductase 1 at the messenger RNA levels by 2- to 12-fold and at the protein levels by 2- to 6-fold in human islets. Increased expression of antioxidant enzymes was seen in beta cells of islets as shown by immunofluorescent staining. Curcuminoids also increased the islet content of glutathione (a product of the modulatory subunit of gamma-glutamyl-cysteine ligase) and the basal insulin secretion and protected them from oxidative stress.


CONCLUSIONS
Our observations suggest that curcumin or its analogues could be used to induce cellular defense against oxidative stress and improve islet transplantation outcomes.
Balamurugan
A N
AN
Diabetes Institute for Immunology and Transplantation, University of Minnesota, MN, USA.
Akhov
Leonid
L
Selvaraj
Gopalan
G
Pugazhenthi
Subbiah
S
D000975:Antioxidants / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003474:Curcumin / Q000031:analogs & derivatives / Q000494:pharmacology*; D036381:Diarylheptanoids; D004798:Enzymes / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005721:Glutamate-Cysteine Ligase / Q000235:genetics / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016381:Islets of Langerhans Transplantation / Q000379:methods; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000975:Antioxidants; D036381:Diarylheptanoids; D004798:Enzymes; D007328:Insulin; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione; D003474:Curcumin; C050229:demethoxycurcumin