The Experts below are selected from a list of 7158 Experts worldwide ranked by ideXlab platform
Hanzhong Feng - One of the best experts on this subject based on the ideXlab platform.
-
carbonic anhydrase iii contributes to Fatigue Tolerance and recovery of skeletal muscle
Biophysical Journal, 2014Co-Authors: Hanzhong Feng, J P JinAbstract:Carbonic anhydrase III (CA3) is a metabolic enzyme with a potential role in regulating intracellular pH. CA3 is highly expressed in slow twitch skeletal muscles. Here we demonstrated that mouse tibialis anterior (TA), a fast twitch muscle, also expresses a high level of CA3 while its myofilament protein contents were similar to that of CA3-negative extensor digitorum longus (EDL) muscle. To investigate the function of CA3 in muscle contractility and Tolerance to Fatigue, we studied skeletal muscles of CA3 knockout (Car3-/-) mice. Sciatic nerve stimulation-generated in situ contractility of EDL and TA muscles were examined in comparison with wild type controls. The results of isometric twitch and tetanic contractions showed no significant difference between TA and EDL muscle of wild type mice or between Car3-/- and wild type TA muscles. Nonetheless, intermittent Fatigue treatment revealed faster Fatigue and slower recovery of wild type TA muscle than that of wild type EDL muscle. Car3-/- TA muscle exhibited slower and less Fatigue but also slower recovery than that of wild type TA muscle, whereas the ultimate level of force recovery was unchanged. It is suggested that CA3 increases the sensitivity of muscle to Fatigue, which might serve as an acute physiological protection. In the meantime, Western-blot detected a low molecular weight fast troponin T (TnT) variant specifically in TA muscle of adult Car3-/- mice, suggesting a chronically adaptive response through alternative RNA splicing. The role of CA3 in Fatigue Tolerance and recovery of skeletal muscle suggests a molecular therapeutic target for functional enhancement.
-
fast to slow fiber type switch increases Fatigue resistance as a compensatory adaptation in gsα deficient soleus muscle
Biophysical Journal, 2010Co-Authors: Hanzhong Feng, Min Chen, Lee S Weinstein, J P JinAbstract:Genetically modified mice with Gsα-specific deficiency in skeletal muscle showed reduced glucose Tolerance, muscle atrophy and force reduction, along with a fast-to-slow fiber type switch (Chen et al., AJP 296:C930-40, 2009). We further investigated a hypothesis that the switching to more slow fibers is an adaptive response with functional significance. Corresponding to the muscle type switch evident by myosin isotyping, the thin filament regulatory proteins troponin T and troponin I both had significant changes to their slow isoforms in the atrophic soleus muscle of 3-month-old Gsα-deficient mice. This fiber type switching progressed and soleus muscles of one-year-old Gsα-deficient mice expressed only slow isoforms of troponin. Functional characterization of soleus muscle of 3-month-old Gsα-deficient mice showed slower contractile and relaxation velocity in twitch and tetanic contractions than wild type controls. Examination of Fatigue Tolerance showed that Gsα-deficient soleus muscle was more resistant to intermittent Fatigue stimulation with faster and better recovery as compared with wild type controls. Our results suggest that fast-to-slow type switch improves Fatigue resistance of skeletal muscle as a compensatory adaptation to muscle glucose inTolerance and atrophy in Gsα-deficiency, suggesting a mechanism for improving muscle function in diabetic patients.
-
deletion of a genomic segment containing the cardiac troponin i gene knocks down expression of the slow troponin t gene and impairs Fatigue Tolerance of diaphragm muscle
Journal of Biological Chemistry, 2009Co-Authors: Hanzhong Feng, Bin Wei, Jian Ping JinAbstract:The loss of slow skeletal muscle troponin T (TnT) results in a recessive nemaline myopathy in the Amish featured with lethal respiratory failure. The genes encoding slow TnT and cardiac troponin I (TnI) are closely linked. Ex vivo promoter analysis suggested that the 5'-enhancer region of the slow TnT gene overlaps with the structure of the upstream cardiac TnI gene. Using transgenic expression of exogenous cardiac TnI to rescue the postnatal lethality of a mouse line in which the entire cardiac TnI gene was deleted, we investigated the effect of enhancer deletion on slow TnT gene expression in vivo and functional consequences. The levels of slow TnT mRNA and protein were significantly reduced in the diaphragm muscle of adult double transgenic mice. The slow TnT-deficient (ssTnT-KD) diaphragm muscle exhibited atrophy and decreased ratios of slow versus fast isoforms of TnT, TnI, and myosin. Consistent with the changes toward more fast myofilament contents, ssTnT-KD diaphragm muscle required stimulation at higher frequency for optimal tetanic force production. The ssTnT-KD diaphragm muscle also exhibited significantly reduced Fatigue Tolerance, showing faster and more declines of force with slower and less recovery from Fatigue as compared with the wild type controls. The natural switch to more slow fiber contents during aging was partially blunted in the ssTnT-KD skeletal muscle. The data demonstrated a critical role of slow TnT in diaphragm function and in the pathogenesis and pathophysiology of Amish nemaline myopathy.
-
Decreased Fatigue Tolerance In Diaphragm Muscle Of Slow Troponin T Knockdown Mice
Biophysical Journal, 2009Co-Authors: Hanzhong Feng, Bin Wei, Jian Ping JinAbstract:The loss of slow skeletal muscle troponin T (TnT) results in a severe type of nemaline myopathy in the Amish (ANM). The genes encoding TnT and troponin I (TnI) are closely linked in pairs in which the 5′-enhancer region of the slow TnT gene overlaps with the cardiac TnI gene. In a mouse line with the entire cardiac TnI gene deleted, a partial destruction of the slow TnT gene promoter produces a knockdown effect. By crossing with transgenic mouse lines that over-express a core structure of cardiac TnI (cTnI-ND) under the control of cloned alpha-MHC promoter, we rescued the postnatal lethality of the cardiac TnI gene-deleted mice with no detrimental cardiac phenotypes or leaking expression in non-cardiac tissues. The double transgenic mice exhibited decreased expression of slow TnT mRNA and protein in adult diaphragm muscle. Functional analysis of isolated muscle strips showed that the slow TnT deficient (sTnT-KD) diaphragm had significantly decreased Fatigue Tolerance evident by the faster decrease in force and slower rate of recovery as compared with that in wild type controls. As a consequence of slow TnT deficiency, the sTnT-KD diaphragm muscle contained a higher proportion of fast TnT, decreased slow TnI with increased fast TnI, and decreased type I myosin with increased type II myosin. Consistent with the switch toward fast myofilament contents, the sTnT-KD diaphragm muscle produced higher specific tension in twitch and tetanic contractions as well as shorter time to develop peak tension in twitch contractions. The decreased Fatigue Tolerance of sTnT-KD diaphragm muscle explains the terminal respiratory failure seen in virtually all ANM patients and this double transgenic mouse model provides a useful experimental system to study the pathogenesis and treatment of ANM.
Jian Ping Jin - One of the best experts on this subject based on the ideXlab platform.
-
deletion of a genomic segment containing the cardiac troponin i gene knocks down expression of the slow troponin t gene and impairs Fatigue Tolerance of diaphragm muscle
Journal of Biological Chemistry, 2009Co-Authors: Hanzhong Feng, Bin Wei, Jian Ping JinAbstract:The loss of slow skeletal muscle troponin T (TnT) results in a recessive nemaline myopathy in the Amish featured with lethal respiratory failure. The genes encoding slow TnT and cardiac troponin I (TnI) are closely linked. Ex vivo promoter analysis suggested that the 5'-enhancer region of the slow TnT gene overlaps with the structure of the upstream cardiac TnI gene. Using transgenic expression of exogenous cardiac TnI to rescue the postnatal lethality of a mouse line in which the entire cardiac TnI gene was deleted, we investigated the effect of enhancer deletion on slow TnT gene expression in vivo and functional consequences. The levels of slow TnT mRNA and protein were significantly reduced in the diaphragm muscle of adult double transgenic mice. The slow TnT-deficient (ssTnT-KD) diaphragm muscle exhibited atrophy and decreased ratios of slow versus fast isoforms of TnT, TnI, and myosin. Consistent with the changes toward more fast myofilament contents, ssTnT-KD diaphragm muscle required stimulation at higher frequency for optimal tetanic force production. The ssTnT-KD diaphragm muscle also exhibited significantly reduced Fatigue Tolerance, showing faster and more declines of force with slower and less recovery from Fatigue as compared with the wild type controls. The natural switch to more slow fiber contents during aging was partially blunted in the ssTnT-KD skeletal muscle. The data demonstrated a critical role of slow TnT in diaphragm function and in the pathogenesis and pathophysiology of Amish nemaline myopathy.
-
Decreased Fatigue Tolerance In Diaphragm Muscle Of Slow Troponin T Knockdown Mice
Biophysical Journal, 2009Co-Authors: Hanzhong Feng, Bin Wei, Jian Ping JinAbstract:The loss of slow skeletal muscle troponin T (TnT) results in a severe type of nemaline myopathy in the Amish (ANM). The genes encoding TnT and troponin I (TnI) are closely linked in pairs in which the 5′-enhancer region of the slow TnT gene overlaps with the cardiac TnI gene. In a mouse line with the entire cardiac TnI gene deleted, a partial destruction of the slow TnT gene promoter produces a knockdown effect. By crossing with transgenic mouse lines that over-express a core structure of cardiac TnI (cTnI-ND) under the control of cloned alpha-MHC promoter, we rescued the postnatal lethality of the cardiac TnI gene-deleted mice with no detrimental cardiac phenotypes or leaking expression in non-cardiac tissues. The double transgenic mice exhibited decreased expression of slow TnT mRNA and protein in adult diaphragm muscle. Functional analysis of isolated muscle strips showed that the slow TnT deficient (sTnT-KD) diaphragm had significantly decreased Fatigue Tolerance evident by the faster decrease in force and slower rate of recovery as compared with that in wild type controls. As a consequence of slow TnT deficiency, the sTnT-KD diaphragm muscle contained a higher proportion of fast TnT, decreased slow TnI with increased fast TnI, and decreased type I myosin with increased type II myosin. Consistent with the switch toward fast myofilament contents, the sTnT-KD diaphragm muscle produced higher specific tension in twitch and tetanic contractions as well as shorter time to develop peak tension in twitch contractions. The decreased Fatigue Tolerance of sTnT-KD diaphragm muscle explains the terminal respiratory failure seen in virtually all ANM patients and this double transgenic mouse model provides a useful experimental system to study the pathogenesis and treatment of ANM.
Bin Wei - One of the best experts on this subject based on the ideXlab platform.
-
deletion of a genomic segment containing the cardiac troponin i gene knocks down expression of the slow troponin t gene and impairs Fatigue Tolerance of diaphragm muscle
Journal of Biological Chemistry, 2009Co-Authors: Hanzhong Feng, Bin Wei, Jian Ping JinAbstract:The loss of slow skeletal muscle troponin T (TnT) results in a recessive nemaline myopathy in the Amish featured with lethal respiratory failure. The genes encoding slow TnT and cardiac troponin I (TnI) are closely linked. Ex vivo promoter analysis suggested that the 5'-enhancer region of the slow TnT gene overlaps with the structure of the upstream cardiac TnI gene. Using transgenic expression of exogenous cardiac TnI to rescue the postnatal lethality of a mouse line in which the entire cardiac TnI gene was deleted, we investigated the effect of enhancer deletion on slow TnT gene expression in vivo and functional consequences. The levels of slow TnT mRNA and protein were significantly reduced in the diaphragm muscle of adult double transgenic mice. The slow TnT-deficient (ssTnT-KD) diaphragm muscle exhibited atrophy and decreased ratios of slow versus fast isoforms of TnT, TnI, and myosin. Consistent with the changes toward more fast myofilament contents, ssTnT-KD diaphragm muscle required stimulation at higher frequency for optimal tetanic force production. The ssTnT-KD diaphragm muscle also exhibited significantly reduced Fatigue Tolerance, showing faster and more declines of force with slower and less recovery from Fatigue as compared with the wild type controls. The natural switch to more slow fiber contents during aging was partially blunted in the ssTnT-KD skeletal muscle. The data demonstrated a critical role of slow TnT in diaphragm function and in the pathogenesis and pathophysiology of Amish nemaline myopathy.
-
Decreased Fatigue Tolerance In Diaphragm Muscle Of Slow Troponin T Knockdown Mice
Biophysical Journal, 2009Co-Authors: Hanzhong Feng, Bin Wei, Jian Ping JinAbstract:The loss of slow skeletal muscle troponin T (TnT) results in a severe type of nemaline myopathy in the Amish (ANM). The genes encoding TnT and troponin I (TnI) are closely linked in pairs in which the 5′-enhancer region of the slow TnT gene overlaps with the cardiac TnI gene. In a mouse line with the entire cardiac TnI gene deleted, a partial destruction of the slow TnT gene promoter produces a knockdown effect. By crossing with transgenic mouse lines that over-express a core structure of cardiac TnI (cTnI-ND) under the control of cloned alpha-MHC promoter, we rescued the postnatal lethality of the cardiac TnI gene-deleted mice with no detrimental cardiac phenotypes or leaking expression in non-cardiac tissues. The double transgenic mice exhibited decreased expression of slow TnT mRNA and protein in adult diaphragm muscle. Functional analysis of isolated muscle strips showed that the slow TnT deficient (sTnT-KD) diaphragm had significantly decreased Fatigue Tolerance evident by the faster decrease in force and slower rate of recovery as compared with that in wild type controls. As a consequence of slow TnT deficiency, the sTnT-KD diaphragm muscle contained a higher proportion of fast TnT, decreased slow TnI with increased fast TnI, and decreased type I myosin with increased type II myosin. Consistent with the switch toward fast myofilament contents, the sTnT-KD diaphragm muscle produced higher specific tension in twitch and tetanic contractions as well as shorter time to develop peak tension in twitch contractions. The decreased Fatigue Tolerance of sTnT-KD diaphragm muscle explains the terminal respiratory failure seen in virtually all ANM patients and this double transgenic mouse model provides a useful experimental system to study the pathogenesis and treatment of ANM.
J P Jin - One of the best experts on this subject based on the ideXlab platform.
-
carbonic anhydrase iii contributes to Fatigue Tolerance and recovery of skeletal muscle
Biophysical Journal, 2014Co-Authors: Hanzhong Feng, J P JinAbstract:Carbonic anhydrase III (CA3) is a metabolic enzyme with a potential role in regulating intracellular pH. CA3 is highly expressed in slow twitch skeletal muscles. Here we demonstrated that mouse tibialis anterior (TA), a fast twitch muscle, also expresses a high level of CA3 while its myofilament protein contents were similar to that of CA3-negative extensor digitorum longus (EDL) muscle. To investigate the function of CA3 in muscle contractility and Tolerance to Fatigue, we studied skeletal muscles of CA3 knockout (Car3-/-) mice. Sciatic nerve stimulation-generated in situ contractility of EDL and TA muscles were examined in comparison with wild type controls. The results of isometric twitch and tetanic contractions showed no significant difference between TA and EDL muscle of wild type mice or between Car3-/- and wild type TA muscles. Nonetheless, intermittent Fatigue treatment revealed faster Fatigue and slower recovery of wild type TA muscle than that of wild type EDL muscle. Car3-/- TA muscle exhibited slower and less Fatigue but also slower recovery than that of wild type TA muscle, whereas the ultimate level of force recovery was unchanged. It is suggested that CA3 increases the sensitivity of muscle to Fatigue, which might serve as an acute physiological protection. In the meantime, Western-blot detected a low molecular weight fast troponin T (TnT) variant specifically in TA muscle of adult Car3-/- mice, suggesting a chronically adaptive response through alternative RNA splicing. The role of CA3 in Fatigue Tolerance and recovery of skeletal muscle suggests a molecular therapeutic target for functional enhancement.
-
fast to slow fiber type switch increases Fatigue resistance as a compensatory adaptation in gsα deficient soleus muscle
Biophysical Journal, 2010Co-Authors: Hanzhong Feng, Min Chen, Lee S Weinstein, J P JinAbstract:Genetically modified mice with Gsα-specific deficiency in skeletal muscle showed reduced glucose Tolerance, muscle atrophy and force reduction, along with a fast-to-slow fiber type switch (Chen et al., AJP 296:C930-40, 2009). We further investigated a hypothesis that the switching to more slow fibers is an adaptive response with functional significance. Corresponding to the muscle type switch evident by myosin isotyping, the thin filament regulatory proteins troponin T and troponin I both had significant changes to their slow isoforms in the atrophic soleus muscle of 3-month-old Gsα-deficient mice. This fiber type switching progressed and soleus muscles of one-year-old Gsα-deficient mice expressed only slow isoforms of troponin. Functional characterization of soleus muscle of 3-month-old Gsα-deficient mice showed slower contractile and relaxation velocity in twitch and tetanic contractions than wild type controls. Examination of Fatigue Tolerance showed that Gsα-deficient soleus muscle was more resistant to intermittent Fatigue stimulation with faster and better recovery as compared with wild type controls. Our results suggest that fast-to-slow type switch improves Fatigue resistance of skeletal muscle as a compensatory adaptation to muscle glucose inTolerance and atrophy in Gsα-deficiency, suggesting a mechanism for improving muscle function in diabetic patients.
Joseph D Bruton - One of the best experts on this subject based on the ideXlab platform.
-
impaired sarcoplasmic reticulum ca2 release is the major cause of Fatigue induced force loss in intact single fibres from human intercostal muscle
The Journal of Physiology, 2020Co-Authors: Karl Olsson, Arthur J Cheng, Mamdoh Alameri, Victoria L Wyckelsma, Eric Rullman, Hakan Westerblad, Johanna T Lanner, Thomas Gustafsson, Joseph D BrutonAbstract:Key points Changes in intramuscular Ca2+ handling contribute to development of Fatigue and disease-related loss of muscle mass and function. To date, no data on human intact living muscle fibres have been described. We manually dissected intact single fibres from human intercostal muscle and simultaneously measured force and myoplasmic free [Ca2+ ] at physiological temperature. Based on their Fatigue resistance, two distinct groups of fibres were distinguished: Fatigue sensitive and Fatigue resistant. Force depression in Fatigue and during recovery was due to impaired sarcoplasmic reticulum Ca2+ release in both groups of fibres. Acidification did not affect force production in unFatigued fibres and did not affect Fatigue development in Fatigue-resistant fibres. The current study provides novel insight into the mechanisms of Fatigue in human intercostal muscle. Abstract Changes in intracellular Ca2+ handling of individual skeletal muscle fibres cause a force depression following physical activity and are also implicated in disease-related loss of function. The relation of intracellular Ca2+ handling with muscle force production and Fatigue Tolerance is best studied in intact living single fibres that allow continuous measurements of force and myoplasmic free [Ca2+ ] during repeated contractions. To this end, manual dissections of human intercostal muscle biopsies were performed to isolate intact single fibres. Based on the ability to maintain tetanic force at >40% of the initial value during 500 fatiguing contractions, fibres were classified as either Fatigue sensitive or Fatigue resistant. Following Fatigue all fibres demonstrated a marked reduction in sarcoplasmic reticulum Ca2+ release, while myofibrillar Ca2+ sensitivity was either unaltered or increased. In unFatigued fibres, acidosis caused a reduction in myofibrillar Ca2+ sensitivity that was offset by increased tetanic myoplasmic free [Ca2+ ] so that force remained unaffected. Acidification did not affect the Fatigue Tolerance of Fatigue-resistant fibres, whereas uncertainties remain whether or not Fatigue-sensitive fibres were affected. Following Fatigue, a prolonged force depression at preferentially low-frequency stimulation was evident in Fatigue-sensitive fibres and this was caused exclusively by an impaired sarcoplasmic reticulum Ca2+ release. We conclude that impaired sarcoplasmic reticulum Ca2+ release is the predominant mechanism of force depression both in the development of, and recovery from, Fatigue in human intercostal muscle.
