Effects of metformin on apoptosis induced by advanced glycation end-products and expressions of caspase-3, Bax and Bcl-2 in human dermal fibroblasts in vitro / 南方医科大学学报

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the effect of metformin in protecting against advanced glycation end products (AGEs)-induced apoptosis in human primary dermal fibroblasts.</p><p><b>METHODS</b>Fibroblasts were exposed to 100, 200, or 300 µg/mL AGEs, 300 µg/mL bovine serum albumin (BSA), or 300 µg/mL AGEs and 1 mmol/L metformin for 24, 48, or 72 h. The exposed cells were examined for cell apoptosis using a cell counting kit. The expressions of caspase-3, Bax and Bcl-2 protein in the fibroblasts treated for 72 h were detected with Western blotting.</p><p><b>RESULTS</b>AGEs exposures caused significant dose- and time-dependent apoptosis in the fibroblasts. A 72-h exposure to 300 µg/mL AGEs resulted in obviously increased apoptosis of the fibroblasts compared to the control group (0.72 ± 0.02 vs 1 ± 0.04, P<0.05), and metformin significantly decreased AGEs-induced apoptosis (0.98 ± 0.02 vs 0.72 ± 0.02, P<0.05). The expressions of caspase-3 and Bax protein were significantly increased (P<0.05) and Bcl-2 protein expression was decreased (P<0.05) with a lowered Bcl-2/Bax ratio in AGEs-treated fibroblasts (P<0.05), and such changes were significantly reversed by metformin treatment (P<0.05).</p><p><b>CONCLUSION</b>Metformin can antagonize AGEs-induced apoptosis in human dermal fibroblasts by regulating the expressions of caspase-3, Bax and Bcl-2.</p>