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[Cardiac metallothionein overexpression improves cardiac contractile function and attenuates oxidative stress in lipopolysaccharide-treated mice].
Zhonghua Xin Xue Guan Bing Za Zhi. 2011 Aug; 39(8):711-6.ZX

Abstract

OBJECTIVE

This study was designed to examine the impact of the antioxidant metallothionein (MT) on cardiac contractile, intracellular Ca(2+) function and oxidative stress in lipopolysaccharide (LPS)-treated mice.

METHODS

Weight and age matched adult male FVB and cardiac-specific MT-overexpressing transgenic mice were injected intraperitoneally with 4 mg/kg Escherichia Coli LPS dissolved in sterile saline or an equivalent volume of pathogen-free saline (control groups). Six hours following LPS or saline injection, cardiac geometry and function were evaluated in anesthetized mice using the 2-D guided M-mode echocardiography. Mechanical and intracellular Ca(2+) properties were examined in hearts. Cell shortening and relengthening were assessed using the following indices: peak shortening (PS)-indicative of the amplitude a cell can shorten during contraction; maximal velocities of cell shortening and relengthening (± dl/dt)-indicative of peak ventricular contractility; time-to-PS (TPS)-indicative of systolic duration; time-to-90% relengthening (TR(90))-indicative of diastolic duration (90% rather 100% relengthening was used to avoid noisy signal at baseline concentration). The 360 nm excitation scan was repeated at the end of the protocol and qualitative changes in intracellular Ca(2+) concentration were inferred from the ratio of fura-2 fluorescence intensity (FFI) at two wavelengths (360/380). Fluorescence decay time was measured as an indicator of the intracellular Ca(2+) clearing rate. Glutathione/glutathione disulfide ratio and ROS generation were detected as the markers of oxidative stress.

RESULTS

Heart rate was increased while EF was reduced in LPS-FVB mice and heart rate was reduced and EF increased in MT-LPS transgenic mice [(528 ± 72) beats/min vs (557 ± 69) beats/min, (66 ± 14)% vs (42 ± 10)%, P < 0.05]. Cardiomyocytes from the LPS treated FVB mice displayed significantly reduced peak shortening (PS) and maximal velocity of shortening/relengthening (±dl/dt) associated with prolonged time-to-90% relengthening (TR(90)), these effects were attenuated in cardiomyocytes from the MT-LPS mice [PS(5 ± 1.1)% vs (7.2 ± 0.8)%, dl/dt(160 ± 15) µm/s vs (212 ± 36) µm/s, -dl/dt (175 ± 32) µm/s vs (208 ± 29) µm/s, TR(90) (0.24 ± 0.03)s vs (0.19 ± 0.02)s, P < 0.05]. LPS treated mice showed significantly reduced peak intracellular Ca(2+) and electrically-stimulated rise in intracellular Ca(2+) as well as prolonged intracellular Ca(2+) decay rate without affecting the basal intracellular Ca(2+) levels, again, these effects were significantly attenuated in MT-LPS transgenic mice. Metallothionein overexpression also ablated oxidative stress [reduced ROS generation and increased glutathione/glutathione disulfide ratio, ROS (0.35 ± 0.08) A/µg protein vs (0.24 ± 0.03) A/µg protein]. GSH/GSSG 2.1 ± 0.2 vs 2.6 ± 0.4, P < 0.05.

CONCLUSION

MT overexpression improved cardiac function and ablated oxidative stress in LPS treated mice.

Authors+Show Affiliations

Department of Cardiology, Provincial Hospital Affiliated to Shandong University, Jinan 250021, China. pengalfie@yahoo.com.cnNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

English Abstract
Journal Article
Research Support, Non-U.S. Gov't

Language

chi

PubMed ID

22169416

Citation

Zhao, Peng, et al. "[Cardiac Metallothionein Overexpression Improves Cardiac Contractile Function and Attenuates Oxidative Stress in Lipopolysaccharide-treated Mice]." Zhonghua Xin Xue Guan Bing Za Zhi, vol. 39, no. 8, 2011, pp. 711-6.
Zhao P, Zhang J, Chu X, et al. [Cardiac metallothionein overexpression improves cardiac contractile function and attenuates oxidative stress in lipopolysaccharide-treated mice]. Zhonghua Xin Xue Guan Bing Za Zhi. 2011;39(8):711-6.
Zhao, P., Zhang, J., Chu, X., Yuan, H. T., Cui, L. Q., & Zhu, X. L. (2011). [Cardiac metallothionein overexpression improves cardiac contractile function and attenuates oxidative stress in lipopolysaccharide-treated mice]. Zhonghua Xin Xue Guan Bing Za Zhi, 39(8), 711-6.
Zhao P, et al. [Cardiac Metallothionein Overexpression Improves Cardiac Contractile Function and Attenuates Oxidative Stress in Lipopolysaccharide-treated Mice]. Zhonghua Xin Xue Guan Bing Za Zhi. 2011;39(8):711-6. PubMed PMID: 22169416.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - [Cardiac metallothionein overexpression improves cardiac contractile function and attenuates oxidative stress in lipopolysaccharide-treated mice]. AU - Zhao,Peng, AU - Zhang,Jie, AU - Chu,Xi, AU - Yuan,Hai-tao, AU - Cui,Lian-qun, AU - Zhu,Xing-lei, PY - 2011/12/16/entrez PY - 2011/12/16/pubmed PY - 2012/6/26/medline SP - 711 EP - 6 JF - Zhonghua xin xue guan bing za zhi JO - Zhonghua Xin Xue Guan Bing Za Zhi VL - 39 IS - 8 N2 - OBJECTIVE: This study was designed to examine the impact of the antioxidant metallothionein (MT) on cardiac contractile, intracellular Ca(2+) function and oxidative stress in lipopolysaccharide (LPS)-treated mice. METHODS: Weight and age matched adult male FVB and cardiac-specific MT-overexpressing transgenic mice were injected intraperitoneally with 4 mg/kg Escherichia Coli LPS dissolved in sterile saline or an equivalent volume of pathogen-free saline (control groups). Six hours following LPS or saline injection, cardiac geometry and function were evaluated in anesthetized mice using the 2-D guided M-mode echocardiography. Mechanical and intracellular Ca(2+) properties were examined in hearts. Cell shortening and relengthening were assessed using the following indices: peak shortening (PS)-indicative of the amplitude a cell can shorten during contraction; maximal velocities of cell shortening and relengthening (± dl/dt)-indicative of peak ventricular contractility; time-to-PS (TPS)-indicative of systolic duration; time-to-90% relengthening (TR(90))-indicative of diastolic duration (90% rather 100% relengthening was used to avoid noisy signal at baseline concentration). The 360 nm excitation scan was repeated at the end of the protocol and qualitative changes in intracellular Ca(2+) concentration were inferred from the ratio of fura-2 fluorescence intensity (FFI) at two wavelengths (360/380). Fluorescence decay time was measured as an indicator of the intracellular Ca(2+) clearing rate. Glutathione/glutathione disulfide ratio and ROS generation were detected as the markers of oxidative stress. RESULTS: Heart rate was increased while EF was reduced in LPS-FVB mice and heart rate was reduced and EF increased in MT-LPS transgenic mice [(528 ± 72) beats/min vs (557 ± 69) beats/min, (66 ± 14)% vs (42 ± 10)%, P < 0.05]. Cardiomyocytes from the LPS treated FVB mice displayed significantly reduced peak shortening (PS) and maximal velocity of shortening/relengthening (±dl/dt) associated with prolonged time-to-90% relengthening (TR(90)), these effects were attenuated in cardiomyocytes from the MT-LPS mice [PS(5 ± 1.1)% vs (7.2 ± 0.8)%, dl/dt(160 ± 15) µm/s vs (212 ± 36) µm/s, -dl/dt (175 ± 32) µm/s vs (208 ± 29) µm/s, TR(90) (0.24 ± 0.03)s vs (0.19 ± 0.02)s, P < 0.05]. LPS treated mice showed significantly reduced peak intracellular Ca(2+) and electrically-stimulated rise in intracellular Ca(2+) as well as prolonged intracellular Ca(2+) decay rate without affecting the basal intracellular Ca(2+) levels, again, these effects were significantly attenuated in MT-LPS transgenic mice. Metallothionein overexpression also ablated oxidative stress [reduced ROS generation and increased glutathione/glutathione disulfide ratio, ROS (0.35 ± 0.08) A/µg protein vs (0.24 ± 0.03) A/µg protein]. GSH/GSSG 2.1 ± 0.2 vs 2.6 ± 0.4, P < 0.05. CONCLUSION: MT overexpression improved cardiac function and ablated oxidative stress in LPS treated mice. SN - 0253-3758 UR - https://www.unboundmedicine.com/medline/citation/22169416/[Cardiac_metallothionein_overexpression_improves_cardiac_contractile_function_and_attenuates_oxidative_stress_in_lipopolysaccharide_treated_mice]_ L2 - http://journal.yiigle.com/LinkIn.do?linkin_type=pubmed&amp;issn=0253-3758&amp;year=2011&amp;vol=39&amp;issue=8&amp;fpage=711 DB - PRIME DP - Unbound Medicine ER -