RGD Reference Report - Curcumin attenuates diabetic nephropathy by inhibiting PKC-alpha and PKC-beta1 activity in streptozotocin-induced type I diabetic rats. - Rat Genome Database

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Curcumin attenuates diabetic nephropathy by inhibiting PKC-alpha and PKC-beta1 activity in streptozotocin-induced type I diabetic rats.

Authors: Soetikno, V  Watanabe, K  Sari, FR  Harima, M  Thandavarayan, RA  Veeraveedu, PT  Arozal, W  Sukumaran, V  Lakshmanan, AP  Arumugam, S  Suzuki, K 
Citation: Soetikno V, etal., Mol Nutr Food Res. 2011 Nov;55(11):1655-65. doi: 10.1002/mnfr.201100080. Epub 2011 Aug 30.
RGD ID: 7243969
Pubmed: PMID:22045654   (View Abstract at PubMed)
DOI: DOI:10.1002/mnfr.201100080   (Journal Full-text)

SCOPE: We hypothesized that curcumin, a potent anti-oxidant, might be beneficial in ameliorating the development of diabetic nephropathy through inhibition of PKC-alpha and PKC-beta1 activity-ERK1/2 pathway. METHODS AND RESULTS: Diabetes was induced by a single intraperitoneal injection of streptozotocin (STZ) (55 mg/kg) in rats. Three weeks after STZ injection, rats were divided into three groups, namely, normal, diabetic and diabetic treated with curcumin at 100 mg/kg/day, p.o., for 8 wk. At 11 wk after STZ injection, diabetic rats exhibited renal dysfunction, as evidenced by reduced creatinine clearance, increased blood urea nitrogen (BUN) and proteinuria, marked increases in lipid peroxidation, NOX4 and p67phox and decrease in anti-oxidant enzyme. All of these abnormalities were significantly reversed by curcumin. Furthermore, the high-glucose-induced PKC-alpha and PKC-beta1 activities and phosphorylated ERK1/2 was significantly diminished by curcumin. Curcumin also attenuated the expression of TGF-beta1, CTGF, osteopontin, p300 and ECM proteins such as fibronectin and type IV collagen. The high-glucose-induced expression of VEGF and its receptor VEGF receptor II (flk-1) was also ameliorated by curcumin. CONCLUSION: These results prove that curcumin produces dual blockade of both PKC-alpha and PKC-beta1 activities, which suggests that curcumin is a potential adjuvant therapy for the prevention and treatment of diabetic nephropathy.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Experimental Diabetes Mellitus  ISOMapk1 (Rattus norvegicus)7243969; 7243969 RGD 
Experimental Diabetes Mellitus  IEP 7243969 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Mapk1  (mitogen activated protein kinase 1)

Genes (Mus musculus)
Mapk1  (mitogen-activated protein kinase 1)

Genes (Homo sapiens)
MAPK1  (mitogen-activated protein kinase 1)


Additional Information