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3D IMAGING OF THE MITOCHONDRIAL REDOX STATE OF RAT HEARTS UNDER NORMAL AND FASTING CONDITIONS.

Xu HN, Zhou R, Moon L, Feng M, Li LZ - J Innov Opt Health Sci (2014)

Bottom Line: No significant change in Fp was found (p = 0.4).The NADH/Fp ratio decreased with a marginal p value (0.076).The experimental observation of NADH decrease induced by dietary restriction in the heart at tissue level has not been reported to our best knowledge.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104, USA ; Britton Chance Laboratory of Redox Imaging, Johnson Research Foundation, Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, PA 19104, USA.

ABSTRACT
The heart requires continuous ATP availability that is generated in the mitochondria. Although studies using the cell culture and perfused organ models have been carried out to investigate the biochemistry in the mitochondria in response to a change in substrate supply, mitochondrial bioenergetics of heart under normal feed or fasting conditions has not been studied at the tissue level with a sub-millimeter spatial resolution either in vivo or ex vivo. Oxidation of many food-derived metabolites to generate ATP in the mitochondria is realized through the NADH/NAD(+) couple acting as a central electron carrier. We employed the Chance redox scanner - the low-temperature fluorescence scanner to image the three-dimensional (3D) spatial distribution of the mitochondrial redox states in heart tissues of rats under normal feeding or an overnight starvation for 14.5 h. Multiple consecutive sections of each heart were imaged to map three redox indices, i.e., NADH, oxidized flavoproteins (Fp, including flavin adenine dinucleotide (FAD)) and the redox ratio NADH/Fp. The imaging results revealed the micro-heterogeneity and the spatial distribution of these redox indices. The quantitative analysis showed that in the fasted hearts the standard deviation of both NADH and Fp, i.e., SD_NADH and SD_Fp, significantly decreased with a p value of 0.032 and 0.045, respectively, indicating that the hearts become relatively more homogeneous after fasting. The fasted hearts contained 28.6% less NADH (p = 0.038). No significant change in Fp was found (p = 0.4). The NADH/Fp ratio decreased with a marginal p value (0.076). The decreased NADH in the fasted hearts is consistent with the cardiac cells' reliance of fatty acids consumption for energy metabolism when glucose becomes scarce. The experimental observation of NADH decrease induced by dietary restriction in the heart at tissue level has not been reported to our best knowledge. The Chance redox scanner demonstrated the feasibility of 3D imaging of the mitochondrial redox state in the heart and provides a useful tool to study heart metabolism and function under normal, dietary-change and pathological conditions at tissue level.

No MeSH data available.


Related in: MedlinePlus

The typical heart redox images of the normally fed rats embedded in the way as shown in Fig. 1(a), section depth: 1600 μm.
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Figure 2: The typical heart redox images of the normally fed rats embedded in the way as shown in Fig. 1(a), section depth: 1600 μm.

Mentions: Figure 2 shows the typical pseudo-colored redox images of a heart section of a normally fed rat. As reflected in the color variations and the histogram display of the distribution of the redox indices, the mitochondrial redox state is heterogeneously distributed across the section. For this particular section (depth: 1600 μm), the area near the base appeared to be more reduced and the majority of the cells had redox ratio NADH/Fp centered around 1 (seen from the corresponding histogram). Micro-heterogeneity of sub-millimeter size is also clearly seen, particularly near the base area. The area that has no NADH or Fp fluorescence signals is the atrium and ventricle.


3D IMAGING OF THE MITOCHONDRIAL REDOX STATE OF RAT HEARTS UNDER NORMAL AND FASTING CONDITIONS.

Xu HN, Zhou R, Moon L, Feng M, Li LZ - J Innov Opt Health Sci (2014)

The typical heart redox images of the normally fed rats embedded in the way as shown in Fig. 1(a), section depth: 1600 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4048726&req=5

Figure 2: The typical heart redox images of the normally fed rats embedded in the way as shown in Fig. 1(a), section depth: 1600 μm.
Mentions: Figure 2 shows the typical pseudo-colored redox images of a heart section of a normally fed rat. As reflected in the color variations and the histogram display of the distribution of the redox indices, the mitochondrial redox state is heterogeneously distributed across the section. For this particular section (depth: 1600 μm), the area near the base appeared to be more reduced and the majority of the cells had redox ratio NADH/Fp centered around 1 (seen from the corresponding histogram). Micro-heterogeneity of sub-millimeter size is also clearly seen, particularly near the base area. The area that has no NADH or Fp fluorescence signals is the atrium and ventricle.

Bottom Line: No significant change in Fp was found (p = 0.4).The NADH/Fp ratio decreased with a marginal p value (0.076).The experimental observation of NADH decrease induced by dietary restriction in the heart at tissue level has not been reported to our best knowledge.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104, USA ; Britton Chance Laboratory of Redox Imaging, Johnson Research Foundation, Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, PA 19104, USA.

ABSTRACT
The heart requires continuous ATP availability that is generated in the mitochondria. Although studies using the cell culture and perfused organ models have been carried out to investigate the biochemistry in the mitochondria in response to a change in substrate supply, mitochondrial bioenergetics of heart under normal feed or fasting conditions has not been studied at the tissue level with a sub-millimeter spatial resolution either in vivo or ex vivo. Oxidation of many food-derived metabolites to generate ATP in the mitochondria is realized through the NADH/NAD(+) couple acting as a central electron carrier. We employed the Chance redox scanner - the low-temperature fluorescence scanner to image the three-dimensional (3D) spatial distribution of the mitochondrial redox states in heart tissues of rats under normal feeding or an overnight starvation for 14.5 h. Multiple consecutive sections of each heart were imaged to map three redox indices, i.e., NADH, oxidized flavoproteins (Fp, including flavin adenine dinucleotide (FAD)) and the redox ratio NADH/Fp. The imaging results revealed the micro-heterogeneity and the spatial distribution of these redox indices. The quantitative analysis showed that in the fasted hearts the standard deviation of both NADH and Fp, i.e., SD_NADH and SD_Fp, significantly decreased with a p value of 0.032 and 0.045, respectively, indicating that the hearts become relatively more homogeneous after fasting. The fasted hearts contained 28.6% less NADH (p = 0.038). No significant change in Fp was found (p = 0.4). The NADH/Fp ratio decreased with a marginal p value (0.076). The decreased NADH in the fasted hearts is consistent with the cardiac cells' reliance of fatty acids consumption for energy metabolism when glucose becomes scarce. The experimental observation of NADH decrease induced by dietary restriction in the heart at tissue level has not been reported to our best knowledge. The Chance redox scanner demonstrated the feasibility of 3D imaging of the mitochondrial redox state in the heart and provides a useful tool to study heart metabolism and function under normal, dietary-change and pathological conditions at tissue level.

No MeSH data available.


Related in: MedlinePlus