TY - JOUR
T1 - Regular aerobic exercise-alleviated dysregulation of CAMKIIa carbonylation to mitigate parkinsonism via homeostasis of apoptosis with autophagy
AU - Liu, Wenfeng
AU - Fu, Rang
AU - Wang, Zhiyuan
AU - Liu, Shaopeng
AU - Tang, Changfa
AU - Li, Li
N1 - Publisher Copyright:
© 2019 American Association of Neuropathologists, Inc.
PY - 2020/1/1
Y1 - 2020/1/1
N2 - This study investigated carbonylation of proteins with oxidative modification profiling in the striatum of aging and Parkinson disease (PD) rats, as well as the long-term effects of regular aerobic exercise on the carbonylation process and the damaging effects of PD vs habitual sedentary behavior. Regular aerobic exercise improved the PD rats' rotational behavior, increased tyrosine hydroxylase expression in both the striatum and substantia nigra pars compacta, and decreased a-synuclein expression significantly. Interestingly, apoptotic nuclei and autophagosomes were increased in the aerobic exercise PD rat striatum. Carbonylated protein Ca2+/calmodulin-dependent protein kinase alpha (CAMKIIa) was present in the middle-aged and aged groups but only in the sedentary, not the exercise, PD rat striatum. Notably, CAMKIIa was characterized by a 4-hydroxynonenal adduct. Regular aerobic exercise upregulated CAMKIIa expression level, activated the CAMK signaling pathway, and promoted the expression of autophagy markers Beclin1 and microtubule-associated proteins 1 A/1B light chain 3II. Aberrant carbonylation of CAMKII initiated age-related changes and might be useful as a potential biomarker of PD. Regular aerobic exercise alleviated protein carbonylation modification of CAMKIIa and regulated the CAMK signaling pathway, thereby affecting and regulating the homeostasis of apoptosis and autophagy in the striatum to alleviate the neurodegenerative process of PD lesions.
AB - This study investigated carbonylation of proteins with oxidative modification profiling in the striatum of aging and Parkinson disease (PD) rats, as well as the long-term effects of regular aerobic exercise on the carbonylation process and the damaging effects of PD vs habitual sedentary behavior. Regular aerobic exercise improved the PD rats' rotational behavior, increased tyrosine hydroxylase expression in both the striatum and substantia nigra pars compacta, and decreased a-synuclein expression significantly. Interestingly, apoptotic nuclei and autophagosomes were increased in the aerobic exercise PD rat striatum. Carbonylated protein Ca2+/calmodulin-dependent protein kinase alpha (CAMKIIa) was present in the middle-aged and aged groups but only in the sedentary, not the exercise, PD rat striatum. Notably, CAMKIIa was characterized by a 4-hydroxynonenal adduct. Regular aerobic exercise upregulated CAMKIIa expression level, activated the CAMK signaling pathway, and promoted the expression of autophagy markers Beclin1 and microtubule-associated proteins 1 A/1B light chain 3II. Aberrant carbonylation of CAMKII initiated age-related changes and might be useful as a potential biomarker of PD. Regular aerobic exercise alleviated protein carbonylation modification of CAMKIIa and regulated the CAMK signaling pathway, thereby affecting and regulating the homeostasis of apoptosis and autophagy in the striatum to alleviate the neurodegenerative process of PD lesions.
KW - Aging
KW - Apoptosis
KW - CAMK signaling pathway
KW - Electrospray ionization-quadrupole-time of flight mass spectrometer (ESIQ- TOF-MS)
KW - Parkinson disease
KW - Posttranslational modification analysis
KW - Regular aerobic exercise
UR - http://www.scopus.com/inward/record.url?scp=85076585552&partnerID=8YFLogxK
U2 - 10.1093/jnen/nlz106
DO - 10.1093/jnen/nlz106
M3 - Article
SN - 0022-3069
VL - 79
SP - 46
EP - 61
JO - Journal of Neuropathology and Experimental Neurology
JF - Journal of Neuropathology and Experimental Neurology
IS - 1
ER -