Activation of the M3AChR and Notch1/HSF1 Signaling Pathway by Choline Alleviates Angiotensin II-Induced Cardiomyocyte Apoptosis

Figure 1

Choline attenuated angiotensin II- (Ang II) induced stimulation of the mitochondrial death pathway and cardiomyocyte apoptosis. (a) 4-Diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) administration blocked the effect of choline on terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling- (TUNEL-) positive neonatal rat ventricular myocytes (NRVMs). Scale bar: 50 μm. (b) The ratio of TUNEL-positive cells to total cells. Data are presented as ( independent experiments). (c) Choline treatment increased the Bcl-2/Bax ratio and inhibited caspase-3 activation. The protective effects of choline were reversed by 4-DAMP. (d, e) Quantification of Bcl-2/Bax and cleaved-caspase-3. Data are presented as ( independent experiments). (f) Representative image and graph showing levels of Omi/high-temperature requirement protein A2 (HtrA2), the second mitochondrial activator of caspases/direct inhibitor of apoptosis-binding protein with low P (Smac/DIABLO), and cytochrome c in the cytosol fraction. Data are presented as ( independent experiments). (g) Representative western blot images and data of Omi/HtrA2, Smac/DIABLO, and cytochrome c in the mitochondrial fraction. Data are presented as ( independent experiments). , , and versus control (CTR); ^#, ^##, and ^### versus Ang II; ^&, ^&&, and ^&&& versus the choline-treated Ang II group.

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