JOURNAL ARTICLE

New mechanism of lipotoxicity in diabetic cardiomyopathy: Deficiency of Endogenous H 2 S Production and ER stress

Runmin Guo, Zijun Wu, Jiamei Jiang, Chang Liu, Bin Wu, Xingyue Li, Teng Li, Hailiang Mo, Songjian He, Shanghai Li, Hai Yan, Ruina Huang, Qiong You, Keng Wu
Mechanisms of Ageing and Development 2017, 162: 46-52
27871808

OBJECTIVE: To investigate the roles and mechanisms of endogenous hydrogen sulfide (H2 S) and endoplasmic reticulum (ER) stress in the development of diabetic cardiomyopathy (DCM).

METHODS: Blood of DCM patients included in the study were collected. The model of DCM rats was established using streptozotocin (STZ) injection. Cardiac lipotoxicity in vitro models were established using 500μM palmitic acid (PA) treatment for 24h in AC16 cardiomyocytes. Endogenous H2 S production in plasma, culture supernatant and heart was measured by sulphur ion-selective electrode assay. Cell viability was tested by using the cell counting kit-8 (CCK-8) kit. Glucose regulated protein (GRP78), CCAAT/enhancer binding protein homologous transcription factor (C/EBP) homologous protein (CHOP), caspase-3 and caspase-12 expressions were measured using western blot analysis. Lipid droplet was evaluated by Oil Red O staining. Apoptosis in hearts of DCM rats was analyzed using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining.

RESULTS: H2 S levels in serum of DCM patients and DCM rats were significant lower, H2 S contents and cystathionine-γ-lyase (CSE) expression in heart tissues of DCM rats were also markedly lower. H2 S levels in supernatants of PA-treated AC16 cardiac cells were decreased. Cardiac lipotoxicity demonstrated by increase in TUNEL positive cells and lipid deposit in vivo and in vitro accompanied by a decrease of H2 S levels. Pretreatment AC16 cells with 100μmol/L of NaHS (a donor of H2 S) could suppress the PA-induced myocardial injury similar to the effects of 4-phenylbutyric acid (4-PBA, an endoplasmic reticulum (ER) stress inhibitor), leading to an increase in cell viability and preventing lipid deposit. Meanwhile, administration diabetic rats with NaHS or 4-PBA alleviated cardiac lipotoxicity, as evidenced by decrease in TUNEL positive cells, cleaved caspase-3 expression and lipid accumulation.

CONCLUSION: Deficiency of endogenous H2 S was involved in lipotoxicity-induced myocardial injury. Exogenous H2 S attenuates PA-induced myocardial injury though inhibition of ER stress.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read
27871808
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"