Hypercholesterolemia downregulates autophagy in the rat heart
Background: We have previously shown that efficiency of ischemic conditioning is diminished in hypercholesterolemia and that autophagy is necessary for cardioprotection. However, it is unknown whether isolated hypercholesterolemia disturbs autophagy or the mammalian target of rapamycin (mTOR) pathwa...
Elmentve itt :
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| Dokumentumtípus: | Cikk |
| Megjelent: |
2017
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| Sorozat: | LIPIDS IN HEALTH AND DISEASE
16 No. 1 |
| Tárgyszavak: | |
| doi: | 10.1186/s12944-017-0455-0 |
| mtmt: | 3192151 |
| Online Access: | http://publicatio.bibl.u-szeged.hu/27947 |
| LEADER | 03123nab a2200325 i 4500 | ||
|---|---|---|---|
| 001 | publ27947 | ||
| 005 | 20230724083249.0 | ||
| 008 | 230724s2017 hu o 0|| Angol d | ||
| 022 | |a 1476-511X | ||
| 024 | 7 | |a 10.1186/s12944-017-0455-0 |2 doi | |
| 024 | 7 | |a 3192151 |2 mtmt | |
| 040 | |a SZTE Publicatio Repozitórium |b hun | ||
| 041 | |a Angol | ||
| 100 | 1 | |a Giricz Zoltán | |
| 245 | 1 | 0 | |a Hypercholesterolemia downregulates autophagy in the rat heart |h [elektronikus dokumentum] / |c Giricz Zoltán |
| 260 | |c 2017 | ||
| 300 | |a 8 | ||
| 490 | 0 | |a LIPIDS IN HEALTH AND DISEASE |v 16 No. 1 | |
| 520 | 3 | |a Background: We have previously shown that efficiency of ischemic conditioning is diminished in hypercholesterolemia and that autophagy is necessary for cardioprotection. However, it is unknown whether isolated hypercholesterolemia disturbs autophagy or the mammalian target of rapamycin (mTOR) pathways. Therefore, we investigated whether isolated hypercholesterolemia modulates cardiac autophagy-related pathways or programmed cell death mechanisms such as apoptosis and necroptosis in rat heart. Methods: Male Wistar rats were fed either normal chow (NORM; n=9) or with 2% cholesterol and 0.25% cholic acid-enriched diet (CHOL; n=9) for 12 weeks. CHOL rats exhibited a 41% increase in plasma total cholesterol level over that of NORM rats (4.09mmol/L vs. 2.89mmol/L) at the end of diet period. Animals were sacrificed, hearts were excised and briefly washed out. Left ventricles were snap-frozen for determination of markers of autophagy, mTOR pathway, apoptosis, and necroptosis by Western blot. Results: Isolated hypercholesterolemia was associated with a significant reduction in expression of cardiac autophagy markers such as LC3-II, Beclin-1, Rubicon and RAB7 as compared to controls. Phosphorylation of ribosomal S6, a surrogate marker for mTOR activity, was increased in CHOL samples. Cleaved caspase-3, a marker of apoptosis, increased in CHOL hearts, while no difference in the expression of necroptotic marker RIP1, RIP3 and MLKL was detected between treatments. Conclusions: This is the first comprehensive analysis of autophagy and programmed cell death pathways of apoptosis and necroptosis in hearts of hypercholesterolemic rats. Our data show that isolated hypercholesterolemia suppresses basal cardiac autophagy and that the decrease in autophagy may be a result of an activated mTOR pathway. Reduced autophagy was accompanied by increased apoptosis, while cardiac necroptosis was not modulated by isolated hypercholesterolemia. Decreased basal autophagy and elevated apoptosis may be responsible for the loss of cardioprotection reported in hypercholesterolemic animals. | |
| 650 | 4 | |a Klinikai orvostan | |
| 700 | 0 | 1 | |a Koncsos Gábor |e aut |
| 700 | 0 | 1 | |a Rajtík Tomáš |e aut |
| 700 | 0 | 1 | |a Varga Zoltán |e aut |
| 700 | 0 | 1 | |a Baranyai Tamás |e aut |
| 700 | 0 | 1 | |a Csonka Csaba |e aut |
| 700 | 0 | 1 | |a Szobi Adrián |e aut |
| 700 | 0 | 1 | |a Adameová Adriana |e aut |
| 700 | 0 | 1 | |a Gottlieb Roberta A. |e aut |
| 700 | 0 | 1 | |a Ferdinandy Péter |e aut |
| 856 | 4 | 0 | |u http://publicatio.bibl.u-szeged.hu/27947/1/giricz.pdf |z Dokumentum-elérés |