Table 1.
PKC isozymes that are implicated in human diseases
| Disease | Main PKC isozyme implicated in the pathology Ref | The pathology associated with PKC |
|---|---|---|
| Cancer | PKCα196 | Proliferation, intravasation & metastasis |
| PKCβ54 | Vasculogenesis and cancer cell invasion | |
| PKCδ30 | Angiogenesis | |
| PKCε197 | Proliferation, pro-survival, metastasis, resistance to chemotherapy | |
| PKCθ58 | Gastrointestinal stromal cell proliferation | |
| PKCη89 | Glioblastomal cancer increased proliferation, resistance to radiation | |
| Diabetic complications | PKCβII2 | Vascular complications |
| PKCβ198,199 | Knockout attenuates obesity and increased glucose transport (role of βI?) | |
| PKCδ60 | Stimulation of islet cell function | |
| Ischemic heart disease | PKCδ mediates injury52,160,192,200 | Increased ROS, decreased ATP generation increased apoptosis and necrosis |
| PKCε is protective; useful for predictive ischemia such as in surgery or organ transplantation4,118,160,195,201 | Protection of mitochondrial functions and proteasomal activity, activation of ALDH2 and reduction of aldehydic load | |
| Heart failure | PKCα202,203 | Decreased cardiac contractility, myofilaments force , uncoupling β adrenergic receptor |
| PKCβII5,108,204 | In rats, decreased proteasomal activity and removal of misfolded proteins in several models, disregulate calcium handling. | |
| PKCβII205–209 | In mice*, overexpression results in hypertrophy or is not required for hypertrophy. It also decreases or increases contractility. | |
| PKCε4,5,35 | Increased fibrosis, fibroblasts proliferation, and inflammation | |
| Psoriasis | PKCδ12,66 | Increased inflammation, increased proliferation, dis-regulation of angiogenesis |
| Pain | PKCγ44 | Key mediator of pain in dorsal root ganglia |
| PKCε44 | Key mediator of pain in spinal cord | |
| Autoimmunity and inflammation | PKCδ210,211 | B cell development, inflammation |
| PKCθ6,212 | Involved in many T cell responses | |
| Stroke | PKCδ41,213–215 | Increased mitochondrial fission, ROS production and decreased blood-brain barrier |
| PKCε41,216 | Cytoprotective, increased cerebral blood flow | |
| Bipolar disorders | PKCα10,11,65,112 | Altered gene expression |
| PKCε63 | Altered neuronal transmission | |
| Asthma and other lung diseases | PKCθ217 | Inflammation, airway hyper-responsiveness |
| PKCδ218 (loss of others may contribute to pathology) |
Eosinophils activation | |
| Parkinson’s disease | PKCδ8,219,220 | Inflammation, neuronal cell death |
Footnote: some work using gene knockout and over-expression in mice is not discussed here, because there are conflicting data on the matter and the explanation for the conflicting is not always clear and is beyond the scope of this review.
*
Whereas studies using rat models find that inhibition of PKCβII is protective from heart failure5,204, other studies using mouse genetic models provide conflicting data205–209. Whether these differences reflect species differences, dose of gene, strain of mice or other reasons remain to be determined.